REVIEW Pit.

∆ Pregnancy
Wednesday, July 28, 2010
12:05 PM Interesting: PARS INTERMEDIA
- structure is a very small, not even bone,
- only few epitherlia lined cysts
PITUITARY GLAND CHANGES and related DISEASES IN PREGNANCY - some adults don’t have it
- Active in fetus/pregnancy
Pituitary Gland Growth ○ Produce MSH hormone (melanocyte stimulating
 Massive growth first 2 decades hormone)
 After, declines in mass throughout rest of life ○ Increase fetus hearing
 Women with G1+ status: larger and upward convexity ○ Darkening of skin color in women
- Postpartum shuts off
19th century autopsy: first time showed enlargement in pregnancy

Different sources say different things in regards to its enlargement:

USMLE source: 100%
Medscape: 30% Important cell types to know for disease states:
LitReview: 136% (with 120% vol. enlargement) Ant.pituitary:
 45% 1st tri enlargement Somatotropes: GH
 Largest during first 3 postpartum days Lactotropes: PRL

After 6 months, regains normal size/shape/volume

Differentiating between NATURAL/benign changes, and ABNORMAL/

pathological states

Pathological states of interest:

1) Prolactinomas
2) Acromegaly
3) Cushings
4) Hypopituitarism
i. Sheenhans syndrome (SS)
ii. Lymphocytic hypophysitis

Prolactinoma and pregnancy

PROLACTINOMAS - Enlargement of pit. expected - does not mean adenmatous pit enlargment
- Prolactinomas that enlarge during pregnancy are uncommon
- Suggestive growth
- Headahce
Prolactin = PRL - Visual field changes
 PRL secreting lactotrophs make up 20% pit. Cells in men/nulliparous women - Gestational Diabetes insipidus (enzyme from placental destroys ADH)

 Lactotroph Hyperplasia: End of pregnancy = 50% pituitary cells - Prolactinomas clinical risk
 Reason: from inhibition of somatrotrophs from GH, and effect of increasing  Microplactinoma: 1.3% risk for enlargment
estrogen  Macroplactinoma: 23.2% when untreated (2.8% with treatment)

 Number lactotrophs decline quickly after deliver --> especiially if no lactation - Common treatment: BROMOCRIPTINE
 Recommended for women that become symptomatic (headache, visual field changes)
 But still high levels 11 months postpartum - never complete regression (25% sat. in  Preferable treatment over surgery
multiparous women)  Transsphenoidal surgery if no response to drug therapy
 APPROACH:
Prolactin and Breasts □ Use bromcoriptine to allow ovulation
- Hig h levesls of estrogen --> increase circulating prolactin □ Discontunie at beginning of pregnancy
- Prolactin prepares breasts for lactation □ Start again if evidence of tumor growth
 1st tri: 20-40 ng/mL (ng=nanogram)
 2nd tri: 50-150 ng/mL - BENEFITS
 3rd tri: 100-400 ng/ML  Often improvement/resolution of hyperprolactinoma after pregnancy
□ Fetal levels mimic mom: 80-500 ng/ML  27-29% resolution
□ INTERESTING: reason for neonatal milk/galactorrhea following birth  Mechanism unknown: speculation regarding vascualr ischemia and necrosis in tumor??

Prolactin and Amnioic Fluid

- Produced at secondary site during pregnancy: DECIDUAL cells of uteroplacental unit  MAIN GOAL: maintain the adenoma away from optic chiasma
- Amniotic fluid in vetro: 4000-6000 ng/ML prolactin ○ No universal accept PRL target levels
- Amniotic fluid term: 200-800 ng/ML
□ Dopamine agonists do not stop this production of decidual prolactin  CONCLUSION:
 Common in females during reproductive age
 Treat restores fertility/results in pregnancies
BACKGROUND  MICROprolactinomas: low risk tumor growth/
- Account for 50% functional pituitary tumors  MACROprolactinomas: planned pregnancy after tumor growth
- Since 1970s, first line treatment: bromocriptine --> control/followed with dopamine agonist therapy (commenced after 1st
- Wome with prolactinomas --> on dopamine --> warned about RAPID RESTORATION OF trimester)
FERTILITY
 So the dopa that they are on acts as contraceptive,
- So when women with PRL-secreting macroadeonoma wishes to become pregnant,
normalization of serum PRL and sig reduc in tumor volume decessary to avoid vital
structure compression

Acromegaly in pregnancy

ACROMEGALY - Acromegaly patients:

○ Menstrual irregulariy/amenorrhea
 Atributed to: compromised gonadotropin producing cells/concurrent
hyperprolactinemia
GH association:  Prolactinlike effects GH may contribute to menstrual irregularity
 Somatotrophs reduced in normal pregnancy
○ Somatotrophs: ant. Pit cells that produce GH - DURING PRGNANCY
○ Constitute 30-40% ant pit cells ○ Increases insulin resistnace --> risk gDM / HTN
○ Respond to GhRH , which then tells cells to release Gh ○ Underlying cardiac issues (cardiomyopathy) become SYMPOTMATIC during preg
 Excess before puberty: gigantism ○ Pregnancy does not usually alter course of acromegaly
 Excess after puberty: acromegaly

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 - DIAGNOSIS
 Paradoxically: iGF1 - increased during pregnancy ○ Diffic to establish in first time pregnancy
 iGF1: insulin-like growth factor 1 ○ Because placent GH high --> results can erroneously indicate acromegaly (false positive)
 Aka 'somatomedin c' 'machano growht factor' ○ Definitive diagnosis may not be possible until after delivery
 Stimulates cell growth/proliferation, inhibits programmed cell death ○ Definitive treatment can usually wait till postpartum
 So GH acts on liver to produce lGF1 --> stimulates systemic body growht in - CLUES
almost every system ○ Increase in pit GH pulsatility
○ Result of GH secretion by syntiotrophoblastic epithelium ○ Placental GH secretion apulsatile
○ Patients with GH deficiency have normal igf1 levels in pregnancy
 Placenta produced variant GH (human growth hormon variant hGH-V) - TREATMENT
 Placent GH increase through term, rapidly declines after delivery ○ Major concern: potential tumor expansion leading to neuro/visual compliactions due to
○ Placent GH --> stim /produc hepatic iGF1 --> suppress pit secretion GH effects of estrogens (growth promiting)
○ Dopamine agonists: control disease in 10% cases
 Placenta also produces GH + iGF1  Bromocriptine
○ If significant tumor enlargemnt --> Transsphenoidal surgery/bromocriptine therapy
○ Women with preexisting acromegaly --> withdraw drug therapy, helps with having
uneventful pregnancy

- BENEFITS:
○ Pregnancy lead to improvement of acromegaly in 3 pregnancies with uncontrolled
acromegalic women (blocking effects of estrogen on IGF1 producing in liver)

CUSHINGS DISEASE Treatment of Cushing's disease during pregnancy

- Not enough women/reports with CD to compare outcome treatments
Pregnancy is rare in patients with Cushing's syndrome (CS) because of hypercortisolemia, - Important facto: severity of hypercortisolemia and stage of gestation
hyperandrogenemia, and/or hyperprolactinemia, leading to impaired fertility (74, 75).
○ ACTH secreting adenomas: transphenoidal surgery
- When surgery cannot be preformed:
- Pregnancy induced exacerbation: unregulated placental CRH secretion
○ metyrapone/Ketoconazole/mitotane
○ Which more active in 3rd tri
○ Metyrapone: 18 live births out of 20 sample study
○ Ketoconazole: IUGR, fatal hypoadrenalism, transient neonatal hypoglycemia
Diagnosis of Cushing's syndrome during pregnancy
- Cases diagnosed during pregnancy: weight gain, hypertension, glucose intolerance, straie ○ Mitotane: teratogenic, therapuetic abortion
○ Straie normal pregnancy: WHITE
○ Straie CS pregnancy: PURPLE
○ Hirsutism/acne --> indicitive of excessive androgren
○ Presence suggest CS: hypokalemia, muscle weakness, patho fractures, purple abomdinal striae Complications in pregnancy: increase HTN (87%), DM (61%), Ppreeclampsia (10%)
- Adrenal adenoma: pulmonary edema (44%)
- Poor wound healing, postop infections
- Diagnostic tests less reliable during gestation Risk to fetus: premature labor (60%), IUGR, perinatal death
○ Usual test (low dose dexamethasone fails to suppres cortisol sec. during pregnancy, so this would
lead to lots of false positives)

- So most of the normal tests are out of the window - SO

○ Imaging studies even suck: most CD by microadenoma, not macro, so 1st it is hard to pick up  If found in 1st, only treat if severe enough
○ Plus growth of pituitary gland can mask visualization of adenoma  If big tumor, cut out in 2nd tri
○ Possibly do adrenal CT scan, but should be avoided if possible (?)  Surgery: treatment of choice for pregant women with CD in 2nd tri
 Delayed diagnosis: 3rd: surgery postponed, METYRAPONE drug of choice
Possible test: Urinary 17-hydroxycorticosteroids
- Unaltered in pregnancy
- Measures urinary free cortisol
- Variation preserved in normal pregnancy --> loss variation early feature cushings

(hypopituitarism) Sheehan i.
ii.
DIAGNOSIS
Typical obstetric history of severe postpartum vag bleeding
Severe hypotnesions or shock for which blood traunsfuion/fluid replacement necessary

Syndrome iii.
iv.
v.
Failure of postpartum lactation
Failure to resume regular menses after delivery
Varyging degrees of ant pituitary failure/partial panhypopituitarism
vi. Empty sella on CT scan/mri

- Described as: postpartum hypopituitarism SYMPTOMS

○ AKA" postpartum pituitary necrosis" --> results in hypopituitarism vii. Nonspecific: weakness, fatgiue, anemia
viii. Severe pit insufficiency: coma/death
- This is due to severe hypotension/shock secondary to masive bleeding during or just after delivery ix. Mean duration between potpartum hemorrhage and clinical manifestations varies from 1 to
- This is most of the time not clinically significant due to deveoped clinical care 33 or 2 to 40 years without a corrleation between severityt
a. In western countries most diagnosed during early postpartum period
6th leading cause of GH deficiency among GH-deficient patients x. SS induced adrencorticol insufficiency results in;
a. Hypotension, orthostatic hypotension, tiredness, hypopigmentation, adrenal crisis
MORE BACKGROUND under stress
- Autoimmunity needs to be established xi. Secondary hypothyroidism
○ Do not show icnreased anti-thyroid peroxidade (TPO) positivity compared to ocntrols
○ Pituitary autoantibody positivity is significantly higher Interesting: subsequent pregnancies reported
○ Antihypothalamus antibodies found in 40% - Pregnancy might imporve hypopituitarism by stimulating pituitary remnant
○ Antipituitary antibodies found in 35% - Thyrotropic functions reconvery spontaneously with pregnancy
 So autoimmunity involving both hypothalamus/pituitary may contribute to delayed pit dysfunction
TREATMENT
 Replacement of deficient hormone(s)
 Glucocortiocid: lifesavining in severe cases
 TSH deficiency: L-t4
 Hypogonadism: estrogen and progesterone in premenopausal women
 GH replacment (improve lipid profile,waist circumerance, fat, carotid artery thickness)

(hypopituitarism) Lymphocytic HYpophysitis

LyH  PRESENTATION
- Autoimmune disoder --> lymphocytic infiltration ○ During pregnancy/postpartum:
- SUBSTYPES  Symptoms of hypopituitarism/mass lession such as headache/visual defects
○ LAH: lymphocytic adenohypophysitis - anterior pit. Dysfunction  Mild hyperprolactinemia/DI
○ Lymphocytic infundibuloneurohypophysitis: character. By DI ○ Often misdiagnosed as Sheehan syndrome in postpartum --> consider LyH in absence of obstetric
○ Lymphocytic panhypophysitis: involvement both ant. and post. pituitary hemorrhage
○ Approx. 30-50% have evidence other endocrine autoimmunity: hasimoto thyroditis, DMI,
pernicious anemia
HORMONE PRODUCTION compromised

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 HORMONE PRODUCTION compromised
 Hypoadrenalism
 Hypothyroidsm LAB EVALUATION
- Low thryoxine, estradiol, cortisol, TSH, FSH, LH, ACTH
IMAGING
○ CT/MRI to exclude mass lesions
 55-57% females LAH present during pregnancy/postpartum with predilection to the last month of ○ Sella is freuqnetly empty, filled only with CSF - sometimes only small tissue fragments
gestation, and the first 2 months postpartum
 No adverse effects on fetus/gestational outcome
 THEORIES  TREATMENT:
○ Increase size of pit. gland may lead to release of pituitary antigens, reason for autoimmune ○ Replacment deficient pituitary hormones
hypophysitis  Glucoroticoids (before levothyroxine)
○ Pituitary gland more accessible to immune system during pregnancy due to hyperestrogenemia  Levothyroxine
(more blood from systemic and less from portal circulation)  Sex steroids
 GH

○ Surgery: only for visual impairments/neuro impairments

 For hyperprolactinemia: BROMOCRIPTINE (also helps improve visual fields)
 Corticosteroids since LyH is autoimmune
□ No consensus for dose length/treatment (high dose preferred)

Spontaneous resulotion reported after delivery for those diagnosed during pregnancy

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