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Pituitary Disorders Jo Choudhry, M.D. PGY-1 The Pituitary

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Pituitary Disorders Jo Choudhry, M.D. PGY-1 The Pituitary Gland Located at the base of the skull Anterior and Posterior lobes Portal connection from the hypothalamus ... – PowerPoint PPT presentation

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Title: Pituitary Disorders Jo Choudhry, M.D. PGY-1 The Pituitary


1
Pituitary Disorders
  • Jo Choudhry, M.D. PGY-1

2
The Pituitary Gland
  • Located at the base of the skull
  • Anterior and Posterior lobes
  • Portal connection from the hypothalamus

3
Anterior Lobe Posterior Lobe
  • Growth hormone (GH)
  • Gondadotrophs (LH/FSH)
  • TSH
  • Prolactin
  • Corticotropin (ACTH)
  • Oxytocin
  • Vasopressin

4
Normal Changes in Pregnancy
  • Anterior lobe size doubles-triples due to
    lactotrophs.
  • Placental estrogens stimulate lactotroph
    proliferation
  • Decreased response to GnRH, dec. LH/FSH
  • Decrease pituitary GH, inc. placental GH
  • Increase CRH (prob. Placental origin) during 2
    3 trimesters
  • 2-4 X increase in ACTH, despite inc. in bound and
    free cortisol.

5
Hyperprolactinemia
  • Causes
  • 1. disruption of dopamine (tumor, trauma,
    infiltrative lesions)
  • 2. hypothyroid (increases TRH)
  • 3. estrogen increase (pregnancy)
  • 4. chest wall burns nueronal effect like
    suckling
  • 5. chronic renal failure, returns to nml after
    transplant
  • 6. drugs (verapamil, H2 blockers, estrogens,
    opiates, dopamine receptor antagonists,
    reserpine, a-methyldopa)

6
Prolactinomas
  • Most common functional pituitary tumor
  • 10 are lactotroph and somatotroph such as GH
    producing
  • Presents with amenorrhea and infertility
  • Prolactinomas lose TRH response
  • Microadenomas lt10mm on MRI
  • Macroadenomas gt10mm

7
Treatment Pregnancy Not Desired
  • Treat only if symptomatic
  • (HA, vision changes)
  • Dopamine agonist (Bromocriptine)
  • 1.25mg qhs 1 wk, then BID
  • If intolerant with nausea, may give vaginally
  • Not recommended for breastfeeding
  • Transspenoidal surgery if unsuccessful

8
Risks of surgery 4.6 post-op
neurologic complication infarction/hemorrhage 2
-10.5 Diabetes Insipidous 8.8 fluid and
electrolyte 2 Cerebrospinal fluid
rhinorrhea 2 Meningitis 3.2 cranial nerve
3,4,or 6 palsies
9
Treatment Pregnancy Desired
  • If macro, shrink size b/f preg with bromocriptine
    (36 will develop neurologic symptoms)
  • If causing major visual defect and unresponsive,
    consider transspenoidal surgery b/f preg.
  • Bromocriptine until
  • preg occurs, then stop.

10
During Pregnancy
  • Visual field check q2-3 mos. and MRI prn
  • If neurologic symptoms occur during preg, usually
    about 14wga, restart treatment.
  • Class B
  • If severe and unresponsive
  • 2nd trimester consider surgery
  • PTL risk
  • 3rd trimester wait until PP

11
Acromegaly
  • 98 GH pituitary adenoma
  • 1/3 of all functional pituitary adenomas
  • Stimulates growth of skin, connective tissue,
    cartilage, bone, and viscera
  • Nitrogen retention, insulin antagonism, and
    lipogenesis

12
Risks of Long Term Excess GH
  • Arthropathy
  • Neuropathy
  • Cardiomyopathy
  • Respiratory obstruction
  • Diabetes Mellitus
  • Hypertension exaterbates cardiomyopathy
  • NOT Reversible
  • increased risk of tumors
  • leiomyomata
  • colon polyps

Reduced overall survival by an average of 10 years
13
Diagnosis
  • Somatomedian-C levels and IGF-1 levels
  • If pregnant special assay to distinguish
    placental GH
  • 70 pitutary GH responds to TRH, placental
    variant does not.

14
Treatment
  • Goal lower the serum insulin-like growth factor
    to normal for age/gender
  • Surgically accessible micro- or Macroadenomas
  • Transspenoidal surgery
  • 2nd Line therapy Somatostatin analogs or
    Dopamine agonists
  • 3rd Line therapy Somatostatin receptor
    antagonist
  • Last resort Radiation

15
Pregnancy and Acromegaly
  • D/C tx with confirmation
  • GH Maternal to Fetal transfer negligible, except
    for glu intolerance.
  • If severe neurologic sympts, try Bromocriptine
  • May not dec. GH, shrink lactotrophs
  • Somatostatin analogs have been used in 3 pts with
    no ill effects to fetus, despite transplacental
    passage.

16
Cushings Disease
  • High ACTH leads to excess glucocorticoid
  • Incidence may be 5-25 per million
  • Women are 3-8X more likely than men

17
Cushings disease
  • Centripetal obesity
  • Moon face buffalo hump
  • Skin atrophy
  • Easily bruised
  • Striae
  • Cutaneous fungal infections
  • Hyperpigmentation
  • Oligo or amenorrhea
  • Hirsutism and Virilization with adrenal tumors

18
Cushings Disease
  • Proximal muscle wasting weakness
  • Osteoporosis
  • Glucose intolerance
  • HTN, hypokalemia
  • Thromboembolism
  • Depression, Psyc
  • Infection
  • Glaucoma

19
Complications if Pregnant
  • Rare due to decreased fertility
  • Premature birth
  • SAB, Stillbirths
  • IUGR
  • Neonatal adrenal insufficiency
  • Maternal HTN, DM, CHF, Death

20
Diagnosis
  • Cushings Syndrome
  • 24 hr urine cortisol excretion
  • If not 3x nml, measure pm salivary cortisol
  • Cushings Disease vs. Syndrome
  • HIGH dose Dexamethasone suppression test (8mg
    overnight)
  • Successful if Pituitary origin

21
Treatment
  • Transsphenoidal surgery
  • Pituitary irradiation
  • Adrenalectomy (Surgical, Mitotane)
  • Nelsons Syndrome expanding intrasellar tumor
    and hyperpigmentation
  • Pregnancy
  • 1st Trimester Surgery
  • 2nd Trimester Adrenal Enzyme Inhibitors vs.
    surgery
  • 3rd Trimester Early delivery, enzyme inhibitors
    until lung maturity

22
Thyrotropin-secreting Adenoma
  • lt1 of all hyperthyroidism cases
  • 25 of adenomas secrete other hormones
  • Goiter, visual defects, menstral irreg,
    galatorrhea
  • Lab
  • Normal or High TSH
  • High total and free T4 and High T3
  • MRI

23
Treatment
  • Transsphenoidal surgery
  • 1/3 Cure
  • 1/3 improvement
  • 1/3 no change
  • Dopamine Agonist
  • Somatostatin Analogue (Octreotide)
  • Works so well, may give before surgery
  • Nausea, diarrhea, bloating, glu intolerance,
    cholelithiasis
  • Do NOT use antithyroid therapy

24
Gonadotroph adenoma
  • Usually considered non-functioning
  • Secrete inefficiently, variably
  • Presents with nuerologic symptoms
  • Difficult to Diagnose
  • Rule out other adenomas
  • Prepubertal girls breast devel, vag. Bleeding
  • Premenopausal amenorrhea, oligo

25
Gonadotroph adenoma vs. menopause and ovarian
failure
  • High FSH with low LH
  • High serum free alpha subunit
  • High estridiol, FSH, thickened endometrium and
    polycystic ovaries

26
Treatment of non-functioning and gonadotrophin
macroadenomas
  • Transsphenoidal surgery
  • /- Radiation

27
Hypopituitarism
  • 76 tumor or treatment of tumor
  • Mass effect of adenoma on other hormones
  • Surgical resection of non-adenomatous tissue
  • Radiation of pituitary
  • Check hormones 6 mos after and then yearly
  • 13 extrapituitary tumor
  • Craniopharyngioma
  • 8 unknown
  • 1 sarcoidosis
  • 0.5 Sheehans syndrome

28
Infiltrative Lesions
  • Hereditary Hemochromatosis
  • Fe deposition in pituitary
  • Gonadotropin deficiency most common
  • Tx repeat phlebotomy
  • Pituitary Apoplexy
  • Sudden hemorrhage into pituitary
  • Severe, sudden HA diplopia hypopituitarism
  • Sudden ACTH def. is life-threatening hypotension
  • Tx surgical decompression

29
Sheehan Syndrome
  • Infarction of Pituitary after substantial blood
    loss during childbirth
  • Incidence 3.6
  • No correlation between severity of hemorrage and
    symptoms
  • Severe recognized days to weeks PP
  • Lethargy, anorexia, weight loss, unable to BF

30
Sheehans Syndrome
  • Typically long interval between obstetric event
    and diagnosis
  • Of 25 cases studied
  • 50 permanent amenorrhea
  • The rest had scanty-rare menses
  • Most lactation was poor to absent
  • Dx MRI empty sella turcica

31
Sheehans and Pregnancy
  • TX with hormones
  • 87 live births
  • 13 SAB
  • 0 Stillbirths
  • 0 Maternal deaths
  • Dont TX
  • 58 live births
  • 42 SAB
  • 1 Stillbirth
  • 3 Maternal deaths

Labor HYDRATION!! IV Cortisol adjusted for
pts state 25-75mg q6 hr
32
Lymphocytic Hypophysitis
  • 22 y/o female died of circulatory collapse 8
    hours after appy. She was 14 mos. PP and had
    developed 2nd amenorrhea.
  • Autopsy lymphocytic infiltration of pituitary
    and thyroid
  • Symptoms HA, lethargy, weight loss,
    hyperprolactinemia

33
Lymphocytic Hypophysis
  • Scheithauer et al, 90
  • 69 women that died during preg or PP
  • 5 had the disease, 4/5 died at 38-41 wga
  • Consider especially if no hemorrhage
  • TX HRT (thyroid, cortisol)

34
Pituitary Necrosis
  • Pregnant Diabetic Patients
  • Due to vascular changes
  • DX severe, midline HA and vomitting in 3rd
    trimester followed by decrease of insulin
    requirements
  • 3/8 cases reported assoc. with fetal and then
    maternal death

35
Central Diabetes Insipidus
  • Polydipsia and Polyuria (2-15 Liters/day)
  • Abrupt onset
  • 30-50 are idiopathic
  • Dec. production by
  • hypothalamus
  • Surgery or Trauma
  • Rare with Sheehans
  • Mild, undetectable degree

36
Dx of Central DI
  • Water Deprivation test
  • Restrict p.o. fluids or administer hypertonic
    saline to increase serum osmolality to 295-300
    mosmol/kg (nml 275-290)
  • Central DI urine osmolality still low and
    returns to normal after administer vasopressin
  • Nephrogenic DI exogenous vasopressin does not
    alter urine osmolality much

37
Pregnancy and Central D.I.
  • Transient D.I. during pregnancy due to acquired
    or hereditary D.I.
  • Latent Unable to sustain during pregnancy
  • Transient Arginine Vasopressin resistant, but
    L-Deamino, 8-D-arginine vasopressin
    (DDAVPDesmopressin) responsive
  • High amounts of placental vasopressinase
  • D.I. antedates pregnancy. Most deteriorate due
    to vasopressinase

38
Treatment of Central D.I.
  • DDAVP (Desmopressin Acetate)
  • Synthetic analog
  • Not catabolized by vasopressinase
  • No vasopressor action
  • Administered intranasally (rec.) or p.o.
  • Titrate 10-20ug qd or bid
  • Safe in pregnancy and breastfeeding

39
References
  • Saunders Maternal-Fetal Medicine 5th Edition
    Chapter 51 ppg. 1083-1094.
  • Weiss, R Refetoff, S Thyrotropin Secreting
    Pituitary Adenomas Up To Date online Jan. 2005
    www.uptodate.com
  • Synder,P. Clinical Manifestations and diagnosis
    of gonadotroph and other clinically
    nonfunctioning adenomas Up To Date online Jan.
    2005 www.uptodate.com
  • Barker,F Klibanski,A Swearingin,B
    Transsphenoidal Surgery for Pituitary Tumors in
    the United States, 1996-2000 Mortality,
    Morbidity, and the Effects of Hospital and
    Surgeon Volume Journal of Clinical Endocrinology
    and Metabolism Vol. 88, No. 10, ppg. 4709-4719.
  • Nieman, L Orth, D Clinical manifestations of
    Cushings Syndrome Up To Date online Jan. 2005
    www.uptodate.com
  • Nieman, L Orth, D Treatment of Cushings
    Syndrome Diminishing adrenal cortisol synthesis.
    Up To Date online Jan. 2005 www.uptodate.com
  • Synder, P Abrahamson, M Management of
    lactotroph adenoma (prolactinoma) during
    pregnancy Up To Date online Jan. 2005
    www.uptodate.com
  • Melmed, S Treatment of Acromegaly Up To Date
    online Jan. 2005 www.uptodate.com
  • Melmed, S Clinical manifestations of acromegaly
    Up To Date online Jan. 2005 www.uptodate.com
  • Synder, P Treatment of Hypopituitarism Up To
    Date online Jan. 2005 www.uptodate.com
  • Abrahamson, M Synder, P Causes of
    hypopituitarism Up To Date online Jan. 2005
    www.uptodate.com
  • Garner, P. Pituitary Disorders of Pregnancy
    Endotext.com Chapter 2A March 2002.
  • Rose, B. Causes of Central Diabetes Insipidous
    Up To Date online Jan. 2005 www.uptodate.com
  • Rose, B. Treatment of Central Diabetes
    Insipidous Up To Date online Jan. 2005
    www.uptodate.com
  • Rose, B Diagnosis of polyuria and Diabetes
    insipidus Up To Date online Jan. 2005
    www.uptodate.com

40
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