Chapter 25 Endocrine disorders(2) 부산백병원 산부인과 R2  강영미
Cushing’s syndrome <ul><li>Adrenal cortex ; three classes of steroid hormones </li></ul><ul><ul><li>Glucocorticoids, miner...
Hyperfunction of adrenal gland(1) <ul><li>Increased glucocorticoids action </li></ul><ul><ul><li>Results in nitrogen wasti...
Hyperfunction of adrenal gland(2) <ul><li>Overproduction of mineralocorticoids </li></ul><ul><ul><li>Arterial hypertension...
cause <ul><li>Six recognized noniatrogenic causes(table 25.3) </li></ul>
 
 
Treatment of ACTH-independent forms of cushing’s syndrome <ul><li>Adrenal cancer </li></ul><ul><ul><li>Mitotane after surg...
Treatment of cushing’s disease(1) <ul><li>Transshenoidal resection ; TOC </li></ul><ul><ul><li>Cure rate ; 80% with microa...
Treatment of cushing’s disease(2) <ul><li>Nelson’s syndrome </li></ul><ul><ul><li>ACTH-secreting pituitary adenoma that de...
Congenital adrenal hyperplasia <ul><li>CAH ; AR disoreders </li></ul><ul><li>Following effects </li></ul><ul><ul><li>Relat...
 
21-hydroxylase deficiency <ul><li>Responsible for over 90% of all cases of CAH </li></ul><ul><li>Diagnosed earlier in affe...
Nonclassic congenital adrenal hyperplasia <ul><li>Partial deficiency in 21-hydroxylation </li></ul><ul><ul><li>Late onset,...
Prenatal diagnosis and treatment <ul><li>21-hydroxylase gene ; located on short arm of chr 6, in the midest of the HLA reg...
Prolactin disorders
Prolactin secretion <ul><li>199 amino acid within human prolactin with MW 23000 daltons </li></ul><ul><li>Three forms ; mo...
 
Hyperprolactinemia-evaluation <ul><li>Plasma levels ; 5-27ng/ml throughout normal mens cycles </li></ul><ul><li>Secreted i...
 
Hyperprolactinemia-physical signs <ul><li>Amenorrhea without galactorrhea(ovulation cessation) ; related following gonadal...
Hyperprolactinemia-imaging techniques <ul><li>In patients with larger micro- and macroadenomas ; higher than 100ng/ml </li...
Pituitary disorders-microadenoma(1) <ul><li>Microadenoma </li></ul><ul><ul><li>Monoclonal in origin </li></ul></ul><ul><ul...
Pituitary diorders-microadenoma(2) <ul><li>Medical treatment </li></ul><ul><ul><li>Ergot alkaloid ; ↑ dopamine levels ↓ PR...
Pituitary disorders-microadenoma(3) <ul><li>Medical treatment </li></ul><ul><ul><li>Pharmacokinetics ; peak serum levels o...
Pituitary adenoma-macroadenoma <ul><li>Bromocriptine ; best initial and potentially long-term treatment option but TSS may...
Metabolic dysfunction drug-induced hyperprolactinemia
Monitoring pituitary adenomas during pregnancy <ul><li>Rarely create cx during pregnancy </li></ul><ul><li>Monitoring c se...
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  1. 1. Chapter 25 Endocrine disorders(2) 부산백병원 산부인과 R2 강영미
  2. 2. Cushing’s syndrome <ul><li>Adrenal cortex ; three classes of steroid hormones </li></ul><ul><ul><li>Glucocorticoids, mineralocorticoids and sex hormones </li></ul></ul>
  3. 3. Hyperfunction of adrenal gland(1) <ul><li>Increased glucocorticoids action </li></ul><ul><ul><li>Results in nitrogen wasting and catabolic state </li></ul></ul><ul><ul><li>Cause muscle weakness, osteoporosis, atrophy of the skin with striae, nonhealing ulceration and recuced immune resistance, glucose intolerance and central obesity </li></ul></ul><ul><li>Overproduction of sex steroid precursors </li></ul><ul><ul><li>Some degree of masculinization in women (hirsutism, acne, oligomenorrhea or amenorrhea) </li></ul></ul><ul><ul><li>Some degree of feminization in men (gynecomastia and impotence) </li></ul></ul>
  4. 4. Hyperfunction of adrenal gland(2) <ul><li>Overproduction of mineralocorticoids </li></ul><ul><ul><li>Arterial hypertension, and hypokalemic alkalosis and pedal edema </li></ul></ul>
  5. 5. cause <ul><li>Six recognized noniatrogenic causes(table 25.3) </li></ul>
  6. 8. Treatment of ACTH-independent forms of cushing’s syndrome <ul><li>Adrenal cancer </li></ul><ul><ul><li>Mitotane after surgery ; benefit in preventing or delaying recurrent disease </li></ul></ul><ul><li>Surgical removal of neoplasm ; TOC </li></ul><ul><ul><li>Unilateral well-circumscribed adenoma ; flank approach is most convenient </li></ul></ul><ul><ul><li>Cure rate following surgical removal of adrenal adenomas ; approaches 100% </li></ul></ul>
  7. 9. Treatment of cushing’s disease(1) <ul><li>Transshenoidal resection ; TOC </li></ul><ul><ul><li>Cure rate ; 80% with microadenomas, less than 50% with macroadenomas </li></ul></ul><ul><li>Medical therapy </li></ul><ul><ul><li>Mitotane ; induce medical adrenalectomy during or after pituitary radiation </li></ul></ul><ul><ul><ul><li>To prepare severely ill patient for surgery and to maintain normal cortisol levels while patient awaits full effect of radiation </li></ul></ul></ul><ul><ul><li>Ketoconazole ; inhibits adrenal steroid biosynthesis at the side arm cleavage and 11b-hydroxylation steps </li></ul></ul><ul><ul><ul><li>Effective for long-term control of hypercortisolism of either pituitary or adrenal origin </li></ul></ul></ul>
  8. 10. Treatment of cushing’s disease(2) <ul><li>Nelson’s syndrome </li></ul><ul><ul><li>ACTH-secreting pituitary adenoma that develops after bilateral adrenalectomy for cushing’s ds </li></ul></ul><ul><ul><li>Complicate 10-50% of bilateral adrenalectomy </li></ul></ul><ul><ul><li>Caused by macroadenoma that produce sellar pressure symptoms of headache, visual field distrubances and opthalmoplegia </li></ul></ul><ul><ul><li>Treatment ; surgical removal or radiation </li></ul></ul>
  9. 11. Congenital adrenal hyperplasia <ul><li>CAH ; AR disoreders </li></ul><ul><li>Following effects </li></ul><ul><ul><li>Relative decrease in cortisol production </li></ul></ul><ul><ul><li>Compensatory increase in ACTH levels </li></ul></ul><ul><ul><li>Hyperplasia of the zona reticularis of the adrenal cortex </li></ul></ul><ul><ul><li>Accumulation of the precursors of the affected enzyme in the bloodstream </li></ul></ul>
  10. 13. 21-hydroxylase deficiency <ul><li>Responsible for over 90% of all cases of CAH </li></ul><ul><li>Diagnosed earlier in affected women than in men </li></ul><ul><ul><li>∵ causes genital virilization </li></ul></ul><ul><ul><li>Diagnosed as virilized newborn females or as rapidly growing masculinized boys at 3 to 7 yrs of age </li></ul></ul><ul><ul><ul><li>Basal follicular phase 17-OHP<200ng/dl ; exclude disorders </li></ul></ul></ul><ul><ul><ul><ul><li>No further testing is required </li></ul></ul></ul></ul><ul><ul><ul><li>Basal 17-OHP>500ng/dl ; confirm </li></ul></ul></ul><ul><ul><ul><ul><li>No need for further testing </li></ul></ul></ul></ul><ul><ul><ul><li>Basal 17-OHP >200 and <500ng/dl ; ACTH stimulation testing </li></ul></ul></ul>
  11. 14. Nonclassic congenital adrenal hyperplasia <ul><li>Partial deficiency in 21-hydroxylation </li></ul><ul><ul><li>Late onset, mild hyperandrogenemia </li></ul></ul><ul><ul><li>No or mild clinical symptoms or signs </li></ul></ul><ul><ul><li>Three phenotypic varieties ; PCOS(39%), hirsutism alone without oligomenorrhea(39%) and cryptic(22%, hyperandrogenism but no hyperandrogenic symptoms) </li></ul></ul>
  12. 15. Prenatal diagnosis and treatment <ul><li>21-hydroxylase gene ; located on short arm of chr 6, in the midest of the HLA region, termed CYP21 </li></ul><ul><li>In families at risk for CAH ; first-trimester prenatal screening – CYP21gene using PCR </li></ul><ul><ul><li>Dexamethasone treatment for all pregnant women at risk of having a child with CAH ; controversial </li></ul></ul><ul><ul><ul><li>20mg/kg in three divided doses administered as soon as pregnancy is recognized and no later than 9 weeks of gestation </li></ul></ul></ul><ul><ul><ul><li>Cross placenta and suppresses ACTH in the fetus </li></ul></ul></ul><ul><ul><ul><li>If female fetus, therapy is continued </li></ul></ul></ul><ul><ul><ul><li>Effectively reduces genital ambiguity but 2/3 pts still requires surgical repair </li></ul></ul></ul>
  13. 16. Prolactin disorders
  14. 17. Prolactin secretion <ul><li>199 amino acid within human prolactin with MW 23000 daltons </li></ul><ul><li>Three forms ; monomer, dimer and multimeric species called little, big, and big-big prolactin </li></ul><ul><ul><li>Little prolactin(MW 23000daltons) ; more than 50% </li></ul></ul><ul><ul><li>Most potent biologic form ; 23000dalton nonglycosylated form of prolactin </li></ul></ul><ul><li>Under inhibitory control mediated by dopamine </li></ul><ul><ul><li>Dopamine ; primary prolactin-inhibiting factor </li></ul></ul><ul><ul><li>GABA & other neuropeptides ; prolactin inhibiting factor </li></ul></ul>
  15. 19. Hyperprolactinemia-evaluation <ul><li>Plasma levels ; 5-27ng/ml throughout normal mens cycles </li></ul><ul><li>Secreted in pulsatile fashion with pulse frequency ranging from 14/24hrs(late follicular phase) to 9/24hrs(luteal phase) </li></ul><ul><li>Diurnal variation ; lowest levels occurring in midmorning, rise 1 hr after onset of sleep and continue to rise until peak values reached between 5-7AM </li></ul><ul><li>Should not drawn soon after patient awakes or after procedures </li></ul><ul><li>Preferably is drawn midmorning and not after stress, venipuncture, breast exam </li></ul><ul><li>Prolactin and TSH ; basic evaluation in infertile women </li></ul>
  16. 21. Hyperprolactinemia-physical signs <ul><li>Amenorrhea without galactorrhea(ovulation cessation) ; related following gonadal and hypothalamic-pituitary effects </li></ul><ul><ul><li>↓ in granulosa cell number and FSH binding , inhibition of granulosa cell 17 b-estradiol production by interfering with FSH action, inadequate luteinizaion and reduced progesterone and suppressive effects of prolactin on GnRH pulsatile release which may mediate most of the anovulatory effects </li></ul></ul><ul><li>Isolated galactorrhea ; within normal range in nearly 50% of such patients </li></ul><ul><li>Amenorrhea and galactorrhea </li></ul><ul><ul><li>2/3 ; have hyperprolactinemia </li></ul></ul><ul><ul><li>(1/3 ; have pituitary adenoma) </li></ul></ul>
  17. 22. Hyperprolactinemia-imaging techniques <ul><li>In patients with larger micro- and macroadenomas ; higher than 100ng/ml </li></ul><ul><li>Levels lower than 100ng/ml ; smaller microadenomas and other suprasellar tumors </li></ul><ul><li>Over 90% of untreated women, microadenomas not enlarge over 4 to 6 yrs period </li></ul><ul><li>PRL correlate with tumor size but both ↓& ↑ in PRL may occur without any change in tumor size </li></ul><ul><li>F/U PRL ↑ or central nervous system symptoms(+) </li></ul><ul><li>-> repeat scanning </li></ul>
  18. 23. Pituitary disorders-microadenoma(1) <ul><li>Microadenoma </li></ul><ul><ul><li>Monoclonal in origin </li></ul></ul><ul><ul><li>Generally be reassured of benign course </li></ul></ul><ul><ul><li>Rarley progress to macroadenoma(7%) </li></ul></ul><ul><li>Expectant management </li></ul><ul><ul><li>In women who no not desire fertility, used for microadenomas and hyperprolactinemia without adenoma </li></ul></ul><ul><ul><li>Estrogen replacement or Ocs in pts with irregular menses or amenorrhea ; prevent osteopenia </li></ul></ul><ul><ul><li>In absence of symptoms, repeat imaging in 12 mon to assess further growth of the microadenoma </li></ul></ul>
  19. 24. Pituitary diorders-microadenoma(2) <ul><li>Medical treatment </li></ul><ul><ul><li>Ergot alkaloid ; ↑ dopamine levels ↓ PRL levels </li></ul></ul><ul><ul><li>Bromocriptine ; ↓PRL synthesis, DNA synthesis , cell multiplication and tumor growth </li></ul></ul><ul><ul><ul><li>Result in normal PRL or return of ovulatory menses in 80-90% of patients </li></ul></ul></ul><ul><ul><ul><li>Excreted via biliary tree, caution in liver ds </li></ul></ul></ul><ul><ul><li>Regimen ; one-half tablet every evening(1.25mg) for 1 week, one-half tablet morning and evening (1.25mg) during second week, one-half tablet in the morning(1.25mg) and full tablet every evening(2.5mg) during third week and one tablet every morning and early evening during the fourth week and thereafter(2.5mg twice a day) </li></ul></ul>
  20. 25. Pituitary disorders-microadenoma(3) <ul><li>Medical treatment </li></ul><ul><ul><li>Pharmacokinetics ; peak serum levels occur 3 hrs after an oral dose with a nadir at 7 hrs, little detectable bromocriptine in serum by 11 to 14 hrs, ∴ required twice-a-day administration </li></ul></ul><ul><ul><li>Adverse effect ; nausea, headaches, hypotension, dizziness, fatigue, and drowsiness, constipation, psychotic reaction </li></ul></ul><ul><ul><li>Cabergoline, another ergot alkaloid </li></ul></ul><ul><ul><ul><li>Very long half-life, given orally once per week </li></ul></ul></ul><ul><ul><ul><li>As effective as bromocriptine in lowering PRL and in reducing tumor size </li></ul></ul></ul>
  21. 26. Pituitary adenoma-macroadenoma <ul><li>Bromocriptine ; best initial and potentially long-term treatment option but TSS may be required </li></ul><ul><ul><li>↓ in PRL and size </li></ul></ul><ul><ul><li>∵ tumor regrowth occurs in over 60% of cases after discontinuation of bromocriptine therapy, long-term therapy is required </li></ul></ul><ul><li>Normalized PRL or resumption of mense ; should not be taken as absolute proof of tumor response to treatment </li></ul><ul><li>Surgical intervention ; tumors that are unresponsive to bromocriptine or that cause persistent visual field loss </li></ul><ul><ul><li>Common recurrence of hyperprolactinemia and tumor growth </li></ul></ul>
  22. 27. Metabolic dysfunction drug-induced hyperprolactinemia
  23. 28. Monitoring pituitary adenomas during pregnancy <ul><li>Rarely create cx during pregnancy </li></ul><ul><li>Monitoring c serial gross visual field exam & fundoscopic exam </li></ul><ul><li>Persistent sx(headaches, visual field deficits) ; MRI advisable </li></ul><ul><li>PRL measurement ; no value </li></ul><ul><li>Bromocriptine ; to resolve sx &visual field deficits in symptomatic pts to allow completion pregnancy before initiation of definitive therapy </li></ul><ul><li>Breast feeding ; not c/Ix in presence of micro- or macroadenoma </li></ul>

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