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

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Pituitary Disorders

• Jo Choudhry, M.D. PGY-1

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The Pituitary Gland

• Located at the base of the skull
• Anterior and Posterior lobes
• Portal connection from the hypothalamus

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Anterior Lobe Posterior Lobe

• Growth hormone (GH)
• Gondadotrophs (LH/FSH)
• TSH
• Prolactin
• Corticotropin (ACTH)

• Oxytocin
• Vasopressin

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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.

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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)

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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

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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

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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
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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.

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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

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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

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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
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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.

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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

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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.

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Cushings Disease

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

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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

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Cushings Disease

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

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Complications if Pregnant

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

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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

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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

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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

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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

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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

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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

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Treatment of non-functioning and gonadotrophin
macroadenomas

• Transsphenoidal surgery
• /- Radiation

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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

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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

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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

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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

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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
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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

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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)

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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

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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

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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

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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

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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

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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

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