Thomas Repas DO FACP CDE Thomas Repas DO FACP CDE UW Hospital and Clinics Department of Medicine UW Hospital and Clinics Department of Medicine Section of Endocrinology, Diabetes & Metabolism Section of Endocrinology, Diabetes & Metabolism H4/568 CSC (5148), 600 Highland Avenue, Madison, WI 53792 H4/568 CSC (5148), 600 Highland Avenue, Madison, WI 53792 Thursday October 13, 2005 Thursday October 13, 2005 Anterior Pituitary Anterior Pituitary Masses and Masses and Hyperprolactinemia Hyperprolactinemia
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Thomas Repas DO FACP CDEThomas Repas DO FACP CDEUW Hospital and Clinics Department of Medicine UW Hospital and Clinics Department of Medicine
Section of Endocrinology, Diabetes & Metabolism Section of Endocrinology, Diabetes & Metabolism
H4/568 CSC (5148), 600 Highland Avenue, Madison, WI 53792 H4/568 CSC (5148), 600 Highland Avenue, Madison, WI 53792
Thursday October 13, 2005Thursday October 13, 2005
Anterior Pituitary Masses Anterior Pituitary Masses and Hyperprolactinemiaand Hyperprolactinemia
ObjectivesObjectives
• Causes of Pituitary Masses• Evaluation of a Pituitary Incidentaloma• Management of Pituitary Neoplasia• Abnormal Anterior Pituitary Function Associated
with Pituitary Masses
• Hyperprolactinemia and Prolactinomas• Causes• Management
I will not discuss in detail…I will not discuss in detail…
• Management of Cushing’s Disease • Management of Acromegaly • Management of Hypopituitarism• Evaluation and Management of Posterior Pituitary
Disorders and Diabetes Insipidus
Normal Pituitary AnatomyNormal Pituitary Anatomy
Lechan RM. Neuroendocrinology of Pituitary Hormone Regulation. Endocrinology and Metabolism Clinics 16:475-501, 1987
Normal Pituitary AnatomyNormal Pituitary Anatomy
Modified from Lechan RM. Neuroendocrinology of Pituitary Hormone Regulation. Endocrinology and Metabolism Clinics 16:475-501, 1987
Development of Human Anterior Development of Human Anterior PituitaryPituitary
Cohen and Radovick, Endocrine Reviews 23: 431-442, 2002
Anterior Pituitary FunctionAnterior Pituitary Function
• Better at visualizing bony structures and calcifications within soft tissues
• Better at determining diagnosis of tumors with calcification, such as germinomas, craniopharyngiomas, and meningiomas
• May be useful when MRI is contraindicated, such as in patients with pacemakers or metallic implants in the brain or eyes
• Disadvantages include: – less optimal soft tissue imaging compared to MRI – use of intravenous contrast media– exposure to radiation
Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm
Craniopharyngioma on CTCraniopharyngioma on CT
Kruskal, J. UpToDate
Clinical EvaluationClinical Evaluation
• All patients with macroadenomas should have formal visual field testing
• In addition to radiographic and hormonal evaluation, patients should be asked and examined for any clinical signs suspicious for pituitary hyperfunction or hypofunction
Hormonal EvaluationHormonal Evaluation
• May include of both basal hormone measurement and dynamic stimulation testing.
• All pituitary masses should have screening 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 or Visual Hormonal or Visual Abnormalities Abnormalities NormalNormal No AbnormalitiesNo Abnormalities
ObserveObserve ObserveObserveTreatmentTreatment
Observation and Follow-upObservation and Follow-up
• If less than 20 mm and no neurologic or hormonal abnormalities: – Monitor for adenoma size, visual changes, and
hormonal hypersecretion in 6 and 12 months, then annually for a few years
• Lesions less than 10 mm and proven to have no hormonal hypersecretion:– Lesions 2 to 4 mm: no further testing required– Lesions 5 to 9 mm: MRI can be done once or twice
over the subsequent two years; if the lesion is stable in this period, the frequency can be decreased
Peter J Snyder MD, “Pituitary incidentaloma” UpToDate November 25, 2003
PharmacotherapyPharmacotherapy
• Most useful in prolactinomas, alone or with other intervention.
• May be used in certain other functioning tumors as adjunctive therapy along with surgical and/or radiotherapy
PharmacotherapyPharmacotherapy
Which pharmacologic option to choose depends on type of tumor:
• Dopamine agonists: bromocriptine, cabergoline- most useful for prolactinomas, less useful for GH secreting adenomas
• Somatostatin analog (Octreotide, Octreotide LAR)- most useful for acromegaly
• Pegvisomant (GH receptor blocker)- useful in acromegaly refractory to somatostatin analogues
• Other: ketoconazole, metyrapone, mitotane- for Cushings disease- use limited by side effects, expense and lack of efficacy
Pituitary SurgeryPituitary Surgery
• Transsphenoidal approach: used for 95% of pituitary tumors
• Endonasal submucosal transseptal approach
• Septal Pushover/Direct Sphenoidotomy
• Endoscopic approach
Indications for Surgery
• Surgery is the first-line treatment of symptomatic pituitary adenomas.
• Useful when medical or radiotherapy fails• Surgery provides prompt relief from excess
hormone secretion and mass effect. • Indicated in pituitary apoplexy with
compressive symptoms
Outcome of Transsphenoidal Outcome of Transsphenoidal SurgerySurgery
Tumor Remission (%) Recurrence at 10 years (%)
Non-functioning Non-functioning adenomaadenoma
Not applicable* 16
GH adenomaGH adenoma Microadenoma
88 1.3
Macroadenoma 65
PRL adenomaPRL adenoma Microadenoma
87 13
Macroadenoma 56
ACTH adenomaACTH adenoma Microadenoma
91 12 (Adults), 42 (Pediatric)
Macroadenoma 65 *Visual improvement occurs in 87% of those with preoperative visual loss.
John A. Jane, Jr., MD Edward R. Laws, Jr., MD, SURGICAL MANAGEMENT OF PITUITARY ADENOMASChapter 13. http://www.endotext.com/neuroendo/neuroendo13/neuroendoframe13.htm
Complications of Complications of Transsphenoidal SurgeryTranssphenoidal Surgery
Minor complicationMinor complication (sinus disease, septal perforations, epistaxis, wound infections and hematomas)
6.5
John A. Jane, Jr., MD Edward R. Laws, Jr., MD, SURGICAL MANAGEMENT OF PITUITARY ADENOMASChapter 13. http://www.endotext.com/neuroendo/neuroendo13/neuroendoframe13.htm
Radiation TherapyRadiation Therapy
• Reserved for patients with larger tumors and/or persistent hormonal hyperfunction despite surgical intervention
Cushing’s Syndrome vs. Cushing’s Cushing’s Syndrome vs. Cushing’s DiseaseDisease
• Cushing’s syndromeCushing’s syndrome is a syndrome due to excess cortisol from pituitary, adrenal or other sources (exogenous glucocorticoids, ectopic ACTH, etc.)
• Cushing’s diseaseCushing’s disease is hypercortisolism due to excess pituitary secretion of ACTH (about 70% of cases of endogenous Cushing’s syndrome)
Hyperprolactinemia Hyperprolactinemia and Prolactinomasand Prolactinomas
ProlactinProlactin
• Human prolactin is a 198 amino acid polypeptide
• Primary function is to enhance breast development during pregnancy and to induce lactation
• Prolactin also binds to specific receptors in the gonads, lymphoid cells, and liver
• Secretion is pulsatile; it increases with sleep, stress, pregnancy, and chest wall stimulation or trauma
ProlactinProlactin
• Secretion of prolactin is under tonic inhibitory control by dopamine, which acts via D2-type receptors located on lactotrophs
• Prolactin production can be stimulated by the hypothalamic peptides, thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP)
Clinical Features of Clinical Features of Hyperprolactinemia/ProlactinomaHyperprolactinemia/Prolactinoma
• Women may present with oligomenorrhea, amenorrhea, galactorrhea or infertility
• Men often have less symptoms than women (sexual dysfunction, visual problems, or headache) and are diagnosed later
• In both sexes, tumor mass effects may cause visual-field defects or headache
Causes of HyperprolactinemiaCauses of Hyperprolactinemia
• Hypothalamic Dopamine Deficiency– Diseases of the hypothalamus( including tumors, arterio-venous
malformations, and inflammatory processes – Drugs (e.g. alpha-methyldopa and reserpine)
• Defective Transport Mechanisms– Section of the pituitary stalk – Pituitary or stalk tumors
Causes of Hyperprolactinemia Causes of Hyperprolactinemia (continued)(continued)
• Lactotroph Insensitivity to Dopamine– Dopamine-receptor-blocking agents: phenothiazines (e.g.
chlorpromazine), butyrophenones (haloperidol), and benzamides (metoclopramide, sulpiride, and domperidone)
• Stimulation of Lactotrophs– Hypothyroidism- increased TRH production (acts as a PRF) – Estrogens: stimulate lactotrophs– Injury to the chest wall: abnormal stimulation of the reflex
associated with the rise in prolactin that is seen normally in lactating women during suckling
REMEMBER:REMEMBER: Not all Not all hyperprolactinemia is due to hyperprolactinemia is due to
a prolactinomaa prolactinoma
REMEMBER:REMEMBER: Not all Not all hyperprolactinemia is due to hyperprolactinemia is due to
Decrease in Size of Prolactinoma Decrease in Size of Prolactinoma after Bromocriptine after Bromocriptine
Abrahamson, M. UpToDate
Dopamine AgonistsDopamine Agonists
• Bromocriptine- start low dose at 1.25- 2.5 mg day at night before increasing to 2.5 – 10 mg per day in divided doses. Take with food to reduce side effects.
• Cabergoline- more effective and with less side effects than Bromocriptine but also more expensive- given once or twice a week with a starting dose of 0.25 mg 2 x week
Titrate these based on prolactin levels and tolerability
ConclusionConclusion
• Pituitary microadenomas are common, not all are of clinical concern
• ALL pituitary tumors require evaluation of hormonal status
• Follow up and monitoring will depend on size and other features of tumor
• Dopamine agonists are the treatment of choice for most prolactinomas
• Surgical intervention is initial TOC for large tumors and other hyperfunctional tumors (GH, ACTH secreting)
• Not every patient with hyperprolactinemia has a prolactinoma!!!