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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. Growth hormone (GH) Gondadotrophs (LH/FSH) TSH Prolactin Corticotropin (ACTH). Oxytocin Vasopressin.

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pituitary disorders

Pituitary Disorders

Jo Choudhry, M.D. PGY-1

the pituitary gland
The Pituitary Gland
  • Located at the base of the skull
  • Anterior and Posterior lobes
  • Portal connection from the hypothalamus
anterior lobe posterior lobe
Growth hormone (GH)

Gondadotrophs (LH/FSH)

TSH

Prolactin

Corticotropin (ACTH)

Oxytocin

Vasopressin

Anterior Lobe Posterior Lobe
normal changes in pregnancy
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.
hyperprolactinemia
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)
prolactinomas
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 <10mm on MRI
  • Macroadenomas >10mm
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

Treatment Pregnancy Not Desired
slide8

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

treatment pregnancy desired
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.

during pregnancy
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
acromegaly
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
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

Risks of Long Term Excess GH

Reduced overall survival by an average of 10 years

diagnosis
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.
treatment
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
pregnancy and acromegaly
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.
cushing s disease
Cushing’s Disease
  • High ACTH leads to excess glucocorticoid
  • Incidence may be 5-25 per million
  • Women are 3-8X more likely than men
cushing s disease1
Cushing’s 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
cushing s disease2
Cushing’s Disease
  • Proximal muscle wasting & weakness
  • Osteoporosis
  • Glucose intolerance
  • HTN, hypokalemia
  • Thromboembolism
  • Depression, Psyc
  • Infection
  • Glaucoma
complications if pregnant
Complications if Pregnant

Rare due to decreased fertility

  • Premature birth
  • SAB, Stillbirths
  • IUGR
  • Neonatal adrenal insufficiency
  • Maternal: HTN, DM, CHF, Death
diagnosis1
Diagnosis

Cushing’s Syndrome:

  • 24 hr urine cortisol excretion
  • If not 3x nml, measure pm salivary cortisol

Cushing’s Disease vs. Syndrome:

  • HIGH dose Dexamethasone suppression test (8mg overnight)
    • Successful if Pituitary origin
treatment1
Treatment
  • Transsphenoidal surgery
  • Pituitary irradiation
  • Adrenalectomy (Surgical, Mitotane)
    • Nelson’s 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
thyrotropin secreting adenoma
Thyrotropin-secreting Adenoma
  • <1% 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

treatment2
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
gonadotroph adenoma
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
gonadotroph adenoma vs menopause and ovarian failure
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
hypopituitarism
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% Sheehan’s syndrome
infiltrative lesions
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
sheehan syndrome
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
sheehan s syndrome
Sheehan’s 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
sheehan s and pregnancy
TX with hormones

87% live births

13% SAB

0 Stillbirths

0 Maternal deaths

Don’t TX

58% live births

42% SAB

1 Stillbirth

3 Maternal deaths

Sheehan’s and Pregnancy

Labor: HYDRATION!!

IV Cortisol: adjusted for pt’s state 25-75mg q6 hr

lymphocytic hypophysitis
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

lymphocytic hypophysis
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)
pituitary necrosis
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
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 Sheehan’s

Mild, undetectable degree

Central Diabetes Insipidus
dx of central di
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
pregnancy and central d i
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 (DDAVP=Desmopressin) responsive
    • High amounts of placental vasopressinase
  • D.I. antedates pregnancy. Most deteriorate due to vasopressinase
treatment of central d i
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
references
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 Cushing’s Syndrome; Up To Date online; Jan. 2005; www.uptodate.com
  • Nieman, L; Orth, D; Treatment of Cushing’s 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