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Hyperandrogenism ppt 25.1.2011

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an overview of the causes and diagnosis of hyperandrogenism

an overview of the causes and diagnosis of hyperandrogenism

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  • 1. Hyperandrogenism and virilizationAssoc Prof Dr Hanifullah Khan Amira, Atiqah, Sufia
  • 2. Objectives1. Androgen2. Virilization3. Causes and patophysiology4. Sign and symptoms5. Question
  • 3. What are androgens? These are generally referred to as male hormones They stimulate or control the development and maintenance of male characteristics They are also the precursors of estrogens
  • 4. Relationships betweenhormones
  • 5. Androgens Testosterone, dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione, and androstenediol The ovaries produce 50% of circulating testosterone, 50% of the androstenedione and 20% of DHEA. The adrenal glands produce all the DHEAS and 80% of the DHEA. The adrenals also secrete 50% of androstenedione and 25% of circulating testosterone. Adrenal androgens increase in response to ACTH stimulation LH stimulates theca cells of the ovaries to secrete androgens
  • 6. Figure 1 Schematic overview of the generation of androgen precursors and their conversion towards active androgens in women. Arlt W Eur J Endocrinol 2006;154:1-11© 2006 Society of the European Journal of Endocrinology
  • 7. Effect of androgens Fat deposition (small breast)  Androgens inhibit the ability of some fat cells to store lipids Muscle mass (heavy mascular mass)  Androgens promote the enlargement of skeletal muscle cells Brain  Enhanced libido.
  • 8. Effects of androgens on skin Pilosebaceous unit (PSU)  Androgens cause excess sebum secretion.  Lesions of the PSU are called acne. Hair  androgens promote the conversion of vellus hairs to coarser terminal hair.  excess growth of terminal hair in a male pattern is called hirsutism.  Follicles shrink causing a receding hair line
  • 9. Hirsutism Excessive male pattern hair growth (face, back, chest, abdomen and inner thighs) Graded with the Ferriman and Gallwey scoring system Hirsutism of rapid onset and growth (over a few months) should raise the concern of an androgen secreting tumour or intersex state Please note that the appearance of hair on the upper lip or mild hirsutism does not necessarily constitute hyperandrogenism, and ethnic origin should be taken into consideration.
  • 10. Ferrimen-Gallwey
  • 11. Facial hair
  • 12. Overview ofandrogenic effects
  • 13. Male esutheon Receding hair lineAcanthosis nigricans Hirsutism
  • 14. Why do women haveandrogens? Androgens have important functions in women ◦ Essential in the production of E2 (in ovary & adipose tissue) ◦ Responsible for dev. & maint. of axillary & pubic hair ◦ Important for libido
  • 15. VirilizationThe development of exaggerated masculinecharacteristics, usually in women, often as a result ofoverproduction of androgensSo, if hyperandrogenism becomesextreme, virilization occurs
  • 16. Symptoms of virilization Symptoms of virilization include ◦ excess facial and body hair (hirsutism), ◦ baldness ◦ acne ◦ deepening of the voice ◦ increased muscularity ◦ an increased sex drive. In women, ◦ the uterus shrinks ◦ the clitoris enlarges (clitoromegaly) ◦ the breasts become smaller ◦ normal menstruation stops (amenorrhea)
  • 17. CAUSES ANDPATHOPHYSIOLOGY
  • 18. Hyperandrogenism Excess of androgens may be caused by: ◦ primary gonadal disorders ◦ primary adrenal disorders ◦ iatrogenic In practice though, the causes are restricted to a few conditions: PCOS Cushing’s syndrome CAH Tumours
  • 19. PCOS ◦ A primary gonadal disorder  Characterized by multiple small cysts within the ovary and by excess androgen production from the ovaries ◦ Increase in LH and androgen secretion ◦ Low aromatase levels (due to  FSH levels) therefore androgens can’t be converted to estrogens in peripheral tissue  Excess androgens converted to testosterone in peripheral tissue
  • 20. Developmental origin of PCOS (adapted from Abbott et al., 2002). Hum. Reprod. Update 2008;14:293-307© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
  • 21. Features of PCOS• Symptoms- • Oligomenorrhoea/ammenorhea • Excessive hair • Infertility • May present with metabolic symptoms• Sign- • Hirsutism • Acne • Acanthosis nigricans (increased velvety skin pigmentation ex at the axilla) • Obesity• Ix – • Clinical/biochemical signs of hyperandrogenism (hirsutism) • Polyystic ovaires by ultrasound
  • 22. Ovaries
  • 23. Other features
  • 24. Metabolic syndrome
  • 25. Acanthosis nigricans
  • 26. Rotterdam criteria 2003 A meeting in Rotterdam crafted compromise criteria ◦ Any two features from  Irregular cycles  Hyperandrogenism  Ultrasound demonstration of polycystic ovaries ◦ (Rotterdam ESHRE/ASRM Sponsored PCOS Consensus Workshop Group: Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81:19) Importantly, the Rotterdam criteria allows for ◦ the previously excluded ovulatory women with features of PCOS ◦ as well as for women with irregular cycles and polycystic ovaries, but without any evidence of androgen excess
  • 27. Primary adrenal disorders Cushing’s disease Congenital adrenal hyperplasia Adrenocortical neoplasms
  • 28. Cushing’s disease ◦ Primary hypothalamic-pituitary disease ◦ Oversecretion of ACTH from pituitary ◦ Presence of adenoma or areas of corticotroph cell hyperplasia in the anterior pituitary ◦ Lead to cortical hyperplasia ◦ Causes hypercortisolism, hyperandrogenism
  • 29. Signs of Cushing’s Hypercortisolism ◦ central obesity, hyperhidrosis ◦ buffalo hump, moon face, striae Hyperandrogenism ◦ hirsutism, male pattern baldness, acne, deepening of the voice,  muscularity, and an  sex drive ◦ uterus shrinks, (clitoromegaly), the breasts become smaller, and normal menstruation stops (amenorrhea)
  • 30. Congenital adrenalhyperplasiaDepends on the nature and severity ofthe enzymytic defect. Onset of clinicalsymptoms can occur in the• Perinatal period• Later childhood• Adulthood (less common)
  • 31. Congenital adrenal hyperplasia◦ Autosomal recessive deficiency of an enzyme in the cortisol synthetic pathways.◦ Cortisol secretion is reduced and feedback leads to increased ACTH secretion to maintain adequate cortisol leading to adrenal hyperplasia.◦ Diversion of the steroid precursors into the androgenic steroid pathways occurs. Thus, 17- hydroxyprogesterone, androstenedione and testosterone levels are increased, leading to virilization.
  • 32. Anterior pituitary Congenital ACT adrenal H Adrenal cortex (bilateral hyperplasia hyperplasia) Cholesterol Pregnolon e Progesteron e 17 - hydroxypregnenolone Dehydroxypiandrosteron 21 e11 - 17 - Androstenediondeoxycortisone hydroxyprogesterone e 21 Corticosterone 11 – deoxycortisol Aldosteron Testosterone e Mineralocorticoids Cortisol Sex steroids Glucocorticoids
  • 33. Adrenocortical neoplasms Adrenocortical neoplasms associated with symptoms of excess of androgen are more likely to be androgen secreting adrenal carcinomas than adenomas. It is also often assoc with hypercortisolism (mixed syndrome) The tumour secretes androgen thus increasing in circulation and converted to testosterone at the peripheral
  • 34. Tumours
  • 35. Androgen secreting tumours May occur at any age. relatively rare. should be suspected when the onset of androgenic symptoms is sudden (i.e., generally <2 yr) and the pace of symptoms is rapid, and when they lead to virilization and masculinization. may be associated with other systemic symptoms including weight loss, anorexia, a feeling of abdominal bloating, back pain.
  • 36. The goals of lab testing 1 2 3 Other causes of androgen Look forDocument excess/ metabolicandrogen irregular abnormalities excess periods to be Eg Glucose/ ruled out Lipids
  • 37. Lab Testosterone and Dehydroepiandrosterone sulphate (DHEAS) ◦ DHEAS hyperandrogenemia of adrenal origin Serum prolactin thyroid stimulating hormone (TSH) Serum 17 hydroxyprogesterone (17-OHP) test –if suspect CAH LH and FSH ( suggestive of PCOS if ratio >2) Lipid profile OGTT ◦ Relying on a fasting glucose level alone is inadequate as it is a poor predictor of impaired glucose tolerance or diabetes
  • 38. TVS
  • 39. Therapy
  • 40. A 22 year old nulligravid women presents to hergynaecologist because of irregular widely spreadmensesCASE SCENARIO
  • 41. History1. What question would like to ask the patient?
  • 42. Examination1. Firstly, what systems would you like to assess2. Secondly, what are the specific signs would you like to elicit?
  • 43. Further clues Menarche was at the age of 14, but she has rarely had regular cycles. For the past year she has had only three complete menses. Once going 6 months between period. She is 165cm and weighs 83kg. She is over weight, with acne and a few dark hairs on her upper lip and chin. She is sexually active and uses condom for contraception.3. What is the likely diagnosis
  • 44. Summary of causes &diagnosis PCOS. ◦ At least two of the following three abnormalities were present: chronic anovulation, clinical or biochemical hyperandrogenism, and polycystic ovaries on ultrasound NCAH. ◦ Clinical hyperandrogenism + increased serum 17OHP or mildly increased serum 17OHP with an increased response to ACTH ( Androgen-secreting tumors. ◦ The finding of an androgen-secreting tumors (ovarian or adrenal) in women with very high serum androgen levels Idiopathic hirsutism. ◦ Normal serum androgen levels (T, free T, and DHEAS) in the presence of normal ovulatory cycles and normal ovaries on ultrasound. Idiopathic hyperandrogenism. ◦ Clinical hyperandrogenism, increased serum androgen levels in the presence of normal ovulatory cycles, and normal ovaries on ultrasound
  • 45. References Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: toward a rational approach. In: Dunaif A, ESHRE/ASRM Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81:19-25. The Rotterdam ESHRE/ASRM-sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41- 47. Azziz R, Carmina E, Dewailly D, et al. Androgen Excess Society. Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endo & Metab 2006; 91(11): 4237-4245. Azziz R, Sanchez LA, Knochenhauer ES, Moran C, Lazenby J, Stephens KC, Taylor K, Boots LR 2004 Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 89:453–462 E. Carmina, F. Rosato, A. Jannì, M. Rizzo, and R. A. Longo Relative Prevalence of Different Androgen Excess Disorders in 950 Women Referred because of Clinical Hyperandrogenism. JCEM 2006 91: 2-6; doi:10.1210/jc.2005-1457
  • 46. Manage wisely