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Endocrine disorders in Pregnancy
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Endocrine disorders in Pregnancy


Endocrine disorders in Pregnancy

Endocrine disorders in Pregnancy

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  • 1. Endocrine disorders inpregnancyPresenter: - Dr. Aneesh. TModerator: - Dr. Pramila Kalra
  • 2. References• Management of Thyroid Dysfunction duringPregnancy and Postpartum: The journal of clinicalendocrinology and metabolism• William’s Obstetrics – 23rd edition• Harrison’s Principles of Internal Medicine – 18th edition• Goodman & Gilmans The Pharmacological Basis ofTherapeutics• Samar Banerjee “Thyroid Disorders in Pregnancy”- Supplement to JAPI • January 2011 • VOL. 59• Mark E. Molitch, MD – “Pituitary and adrenaldisorders in pregnancy”• Beverly M. K. Biller M.D. “Cabergoline - A NewDopamine Agonist for the Therapy of Prolactinoma”
  • 3. Topics coveredI. Thyroid disorders in pregnancyII. Parathyroid disorders in pregnancyIII. Adrenal disorders in pregnancyIV. Pituitary disorders in pregnancy
  • 4. Introduction• Among endocrinopathies inpregnancy, diabetes mellitus – commonest• Thyroid disorders are second• Pituitary, adrenal and parathyroid disordersare less common• Basic pathology – disordered autoimmunity- hypersecretion– Fetal lymphocytes– Fetal stem cells– Fetal DNAReside in maternal endocrineorgans
  • 5. I. THYROID DISORDERS IN PREGNANCYPhysiology• Pregnancy has a substantial impact onmaternal thyroid physiology• Symptoms of thyroid disease duringpregnancy may be confused as physiologicalchanges• 2-5% pregnancies are complicated withthyroid disease
  • 6. • The most important physiological changes arei. Thyroxine binding globulin (TBG) increases –response to estrogen, also half life increases (15min to 3 days)ii. Increase in thyroidstimulatory factorsof placental origin(e.g.. hCG)iii. Decreased iodineavailability –enhanced excretion (increased GFR)iv. BMR increases by 25% in pregnancy
  • 7. Pathophysiology of autoimmunity• Autoantibodies have one or more of thefollowing effects– Stimulation– Inhibition– Inflammation & destruction• Autoimmune phenomenon - follows aprecipitating event– Viral infection– Radiation exposure– Inherent genetic predisposition– Pregnancy itself
  • 8. • Development of antibodies (Fetal – maternal celltrafficking)– Fetal lymphocytes (male fetus>female) enter maternalcirculation and act against the thyroid parenchyma– Maternal microchimerism – SRY region of the malefetal lymphocytes specifically target thyroid cells• More commonly thyroid peroxidase antibodiesoccur (10-20% pregnancies), 50% of thesepatients develop autoimmune thyroiditis• May ultimately develop thyroid failure.
  • 9. A) Hyperthyroidism• Symptomatic thyrotoxicosis occurs in 1/1000or 1/2000 pregnancies• Difficult to differentiate mild disease fromnormal pregnancy symptoms• Elevated T4 with markedly depressed TSH isdiagnostic• Normal T3 and T4 with depressed TSHindicates subclinical hyperthyroidism
  • 10. • Thyrotoxic patients will have high Thyroidstimulating antibodies• However, since autoimmune remission occursdue to pregnancy – and symptoms arerelieved
  • 11. • Propylthiouracil was preferred (trans placentalpassage) to Methimazole (aplasia cutis &embryopathy - choanal atresia)• Propylthiouracil – liver failure in pregnancy• Carbimazole – used safely in EU (rarely associatedwith GI anomalies)Recommendations suggest:• Propylthiouracil (100-600mg/day) – 1st line in 1sttrimester• Methimazole (10-40 mg/day) in the 2nd and 3rd• Both equally efficacious
  • 12. • Dosage to be adjusted to maintain total T4 at1 ½ times upper limit of normal• TFT – every 2-4 weeks• LFT – every 3-4 weeks (Propylthiouracil)• CBC – to assess transientleukopenia/agranulocytosis (Methimazole)• Subtotal thyroidectomy– Severe adverse reactions to medical therapy– Persistent high doses are needed (>450mg PTU or>30 mg MMI)– Non-adherence to therapy
  • 13. Fetal considerations of maternal hyperthyroidism• Thyroid receptor antibodies freely cross placenta• TRAb should be measured by 22 wks of gestation inmothers with– Graves’ disease– h/o Graves’ with I131 therapy prior to pregnancy– Previous neonate with Graves’ disease– Previous documented TRAb• If I131 is given inadvertently– Suggest abortion– Evaluate fetal hypothyroidism
  • 14. Thyroid storm in pregnancy• Rare• Thyroxine induced myocardial effects – precipitatedby preeclamsia, anemia and sepsisTreatment• 1g Propylthiouracil orally/RT, then 200mg Q6H• 500mg – 1g Sodium iodide or 8 drops ofsupersaturated KI• Dexamethasone 2mg iv Q6H for 4 doses• β blockers for tachyarrythmias
  • 15. B) Hypothyroidism• Overt Hypothyroidism – High TSH and low T4• Subclinical – High TSH and normal T4• Hypothyroidism – Adverse outcomes in motherand fetus• Treatment is known to improve obstetricoutcome, however neurodevelopmental longterm effects are not known enough• Potential benefits > risks – Replacement therapyis indicated in subclinical hypothyroidism
  • 16. • Thyroxine requirement in pregnancy is higherthan in non pregnant state.• 30% increase in dosage is needed (TBGincreased)• Hypothyroidism diagnosed duringpregnancy, treated with 50-100 μg/day withTFT at 4-6 week intervals• Dose adjustment with 25-50 μg till TSHmaintained around 2.5 mIU/L (1st trimester)and 3.0 mIU/L (2nd & 3rd trimesters)• Soon after delivery, dose reduction is required
  • 17. • Iodine deficiency may be a cause forhypothyroidism.• Daily requirement of 220 - 250 μg/day has tobe met (not >500 μg/day)Fetal manifestations of maternal hypothyroidism– Decreased school performance– Impaired reading– Reduced IQ• Congenital thyroid screening – mandatory inthe US and EU, not in India.
  • 18. C) Gestational Thyrotoxicosis• Also called Transient hyperthyroidism• Associated with hyperemesis gravidarum• High serum thyroxine and low TSH levels• High βhCG levels – structural similarity to TSH• Gestational trophoblastic disease can alsopresent with hyperthyroidism
  • 19. • Patients with hyperemesis should beevaluated for T4, TSH and TRAb• Anti thyroid drugs – not indicated• β blockers for peripheral manifestations• Anti thyroid drugs are to be given only ifGraves’ disease is diagnosed– Free T4 > 1 ½ times > upper limit of normal– TSH <0.01 μIU/ml
  • 20. D) Post partum thyroiditis• Transient autoimmune thyroiditis• 5-10% of women within a year of childbirth• Women with TRAb and anti-TPO antibodiesbefore pregnancy are more prone to developthis condition• Likelihood of developing post partumthyroiditis is high in Type 1 diabetics andpatients with chronic viral hepatitis
  • 21. Clinical features• 30% chance of eventual permanent hypothyroidism• Post partum depression is associated withit, although not very conclusively
  • 22. Recommended patient profiles for targetedthyroid disease case finding in women seekingpregnancy, or newly pregnant
  • 23. E) Nodular Thyroid disease• Small thyroid nodules – normal in pregnancy• Some studies suggest these nodules turningmalignant• Diagnosis is mainly by sonography & FNAC• FNAC – if nodules > 1cm–5mm to 1cm with suspicious/high risk history
  • 24. • If nodules are detected early• Surgery within 26 wks – after that, surgery canstimulate preterm labourSurgerySuspicious cytologyLymphadenopathyRapid growth
  • 25. • If nodules are detected in the 3rdtrimester, surgery – after delivery.• Papillary and follicular carcinomas arerelatively slow growing & surgery can wait• Radio-iodine therapy at least 4 weeks aftercessation of breastfeeding and the lady askednot to conceive for 6 months to a year
  • 26. II. PARATHYROID DISORDERS• Fetal Calcium needs –300 mg/day• Pregnancy – increasedrenal loss• Increased intestinalabsorption• Serum albumin low,Corrected Ca – normal
  • 27. • Pregnancy has no significant effect on PTHlevels• Vitamin D levels higher – especially 3rdtrimester– Not due to PTH– Due to PTHrP, estradiol, prolactin & placentallactogen all stimulate 1α hydroxylase (renal)
  • 28. A) Hyperparathyroidism• As in non pregnant state – commonestparathyroid adenoma– Hyperemesis– Renal calculi– Psychiatric disorders– Generalized weakness• Pregnancy blunts the effects due to highercalcium requirement by the fetus• Soon after delivery, postpartum hypercalcemiccrisis can occur• Still births and preterm deliveries higher.
  • 29. Management• Elective neck exploration well tolerated evenin 3rd trimester• Asymptomatic women to be given 1 – 1.5gphosphate orally/day in divided doses• Patient in hypercalcemic crisis…– Furosemide to maintain urine output >150ml/hr– Mithramycin at 25μg/kg once and 24 hrs later– Calcitonin 100U every 6 hrs/8 hrs (sc or im)
  • 30. B) Hypoparathyroidism• Commonest cause – post thyroid/parathyroid surgery• Facial muscle spasms, muscle cramps, paraesthesia oflips, tongue, fingers, feet.• Chronic hypocalcemia – multiple bone fractures in theneonateTreatment• Calcitriol is the treatment of choice• Vitamin D – 50,000 – 150,000 U/day to increase levelsof calcitriol• Calcium gluconate 3-5 g/day• Low phosphate diet
  • 31. C) Pregnancy associated osteoporosis• Increased calcium demand and poor oralintake during pregnancy – reduced bonemineral density• Incidence is 4/million pregnancies– Back pain– Hip pain– Difficulty in weight bearing• Treatment is with calcium and Vitamin Dsupplements
  • 32. III. ADRENAL DISORDERS• ACTH and cortisolprogressively increase• Cortisol and progesterone– antagonistic• Mineralocorticoid actionneeded to increase plasmavolume (cortisol &aldosterone)• Protects from natriureticeffect of progesteroneSerial increases in serumcortisol (blue line) and ACTH(red line) during pregnancy.
  • 33. A) Phaeochromocytoma• These chromaffin tumours are rare butdangerous• Maternal death higher – undiagnosedantepartum• Patients can die during labour or duringinduction of anaesthesia• Biggest diagnostic problem is attributinghypertension to PIH/preeclampsia
  • 34. • As the fetus grows, uterus compresses thetumour and cause• Hemorrhage into the neoplasm• Severe hypertension• Hemodynamic compromise• Myocardial infarction• Arrhythmias• Congestive cardiac failure• Index of suspicion must be high – especially• Severe/uncontrolled/paroxysmal hypertension• Orthostatic hypotension• Families associated with MEN-2A• Thyroid nodules – medullary carcinoma (MEN 2A)• Neurofibromatoses
  • 35. • 24 hr urine VMA or Metanephrine to diagnoseadrenal phaeochromocytoma (labetalol &methyl dopa should be stopped)• MIBG (I-metaiodobenzyl guanidine) forextra-adrenal masses• MR imaging
  • 36. Treatment• α blocker – phenoxybenzamine 10 – 30 mg 2-4times a day• β blocker only after α blockade achieved and iftachycardia/arrhythmias persist• Hypertensive emergencies treated withphentolamine.• In the 3rd trimester, C-section + tumourexcision or• Post partum excision of tumour is done
  • 37. B) Cushing syndrome• Commonest cause is long term steroid therapy• Bilateral adrenal hyperplasia due to ACTHproducing adenomas (<1cm microadenomas)• Most patients have corticotropin dependantCushing syndrome and in such cases…PreventspregnancyAnovulationAndrogenexcess
  • 38. NON PREGNANT STATE PREGNANT STATEPituitary adenoma – 75% Pituitary adenoma – 40%Adrenal adenoma – 5-10% Adrenal adenoma – 40%ACTH independent & ectopicACTH tumours – 15 -20%ACTH independent & ectopicACTH tumours – 20%
  • 39. However, diagnosis when it occurs is difficult• Weight gain, fatigue, emotional lability, glucoseintolerance, edema• Serum cortisol levels will be raised anyway (Urinecortisol >3 times normal – can be diagnostic)• Suppression and stimulation tests haven’t been studiedin pregnancyTreatment• Long term therapy not indicated – Resection of theadenoma is definitive• Metyrapone and Ketoconazole can be used till surgeryis planned• Mifepristone cannot be used in pregnancy
  • 40. C) Adrenal Insufficiency• Primary adrenocortical insufficiency(Addison’s) is rare• Secondary to tuberculosis usually andhistoplasmosis rarely• May be a part of “Polyglandular autoimmunesyndrome”• Symptoms again overlap with normalpregnancy – addisonian hyperpigmentationmimics chloasma of pregnancy
  • 41. • Since pregnancy is a hyper-cortisolemic state,low cortisol levels must prompt an ACTHstimulation test• During labour – stress dose of hydrocortisonei.e. 100mg 8th hourly• Shock due to hemorrhage/sepsis – should beruled out
  • 42. D) Primary aldosteronism• Progesterone blocks aldosterone action• Normal pregnancy will ameliorate symptoms• Potassium supplements and antihypertensives• Spironolactone cannot be used –antiandrogenic effects• Tumour resection in 2nd trimester is safe andcurative
  • 43. E) Congenital adrenal hyperplasia• CAH – mutations in genes encodingsteroidogenesis• 21-Hydroxylase deficiency CYP21A–commonest (90-95% of cases in pregnancy)• The spontaneous abortion rate is twice morecommon, congenital anomalies are frequent• CPD due to android pelvis• Fertility is improved with glucocorticoidtherapy – must for conception
  • 44. Fetal risk of CAH• Depends on carrier status of the father• Dexamethasone 20 μg/kg/day upto 1.5 mg dailyin 3 divided doses – starting <9 wks of gestation• Maternal plasma and/or urinary estriol levelsreflect fetal adrenal synthesis – assess efficacy• Only 25% female fetuses affected – treatmentmust be discontinued in male fetus/unaffectedfemale fetus• CVS (9-11 wks) or amniocentesis forandrostenedione/17 (OH) Progesterone (14-16wks) for early gender determination
  • 45. IV. PITUITARY DISORDERS• The pituitary gland enlarges by about 135%• Vision impairment due to this normalenlargement is very rare• Attributed mainly to lactotrophs• The gland involutes post partum – returns tonormal by 6 months
  • 46. A) Prolactinoma• Prolactin secreting tumours are quite common• Microadenoma - <10 mm• Macroadenoma - >10 mm• In normal pregnancy,– Prolactin levels increase markedly– Reaches 10 times normal at term– Levels decrease soon after delivery, despite breastfeeding– Pulsatile bursts of prolactin occur in response tosuckling.
  • 47. • Symptomatic tumour enlargement – rare withmicroadenomas in pregnancy• More frequent with macroadenomas (15-35%)• Headache and vision loss – more common inmacroadenomas and such symptoms shouldbe assessed• Vision testing in each trimester and MRimaging should be done
  • 48. • Microadenomas respond to Bromocriptine• Some studies recommend Cabergoline• Lesser side effects• Longer half life (once a week dose)• However, no adverse effect of bromocriptinehas been known to complicate such apregnancy• Macroadenomas respond on to surgery (trans-nasal endoscopic resection)
  • 49. B) Acromegaly• During normal pregnancy GH levels decrease, asGH like peptides are secreted by the placenta• Acromegaly is due to an acidophillic pituitaryadenoma• Diagnosis is by failure of GH supression with oralGTT• Just like in prolactinomas – vision testing/MRimaging is warranted• Octreotide has shown some benefit• Surgery may be indicated with symptomatictumours
  • 50. C) Diabetes InsipidusCentral Transient Nephrogenic• Central DI – spontaneous – enlarging pituitary adenoma• Transient AVP resistant DI – production of vasopressinase– Acute fatty liver of pregnancy or acute viral hepatitis can worsen DI –hepatic degeneration of vasopressinase is reduced– AVP levels fall – worsens symptoms• Congenital nephrogenic DI is rare – thiazides to be used withextreme caution
  • 51. • Intranasal administration of desmopressin issafe in pregnancy• Dose may be increased if liver disease co-exists in pregnancy• By 4th week post partum, disease usuallyresolves completely
  • 52. D) Sheehan’s syndrome• Pituitary necrosis secondary to ischemia withinhours of delivery• Secondary to hypotension & shock followingobstetric haemorrhage• Physiological gland size increase predisposes toischemic necrosis– Hypotension & tachycardia persists even withadequate blood replenishment– Lactation fails, hypoglycaemia ensues– Delayed symptoms are loss oflibido, amenorrhea, breast atrophy
  • 53. • MRI reveals partial/completely empty sellae• Replacement therapy is the only option• Rare with good obstetric practiseTwo distinct forms have been identified
  • 54. E) Lymphocytic hypophysitis• Autoimmune infiltration of pituitary parenchymaby lymphocytes & plasma cells• Associated with hypopituitarism and mass effects• Imaging cannot distinguish it from pituitaryadenoma• Hormone replacement therapy – usually onlyoption• Spontaneous regression possible – most developpanhypopituitarism• Surgery only indicated to debulk and reduce masssymptoms
  • 55. Take home messages• Physiology of pregnancy alters the course ofmost endocrine disorders• Index of suspicion must be high in pregnancymainly due to overlapping normal symptomsof pregnancy• Thyroid screening in pregnancy isimportant, especially to prevent fetalhypothyroidism
  • 56. Thank you