Hyperandrogenism and virilizationAssoc Prof Dr Hanifullah         Khan  Amira, Atiqah, Sufia
Objectives1.   Androgen2.   Virilization3.   Causes and patophysiology4.   Sign and symptoms5.   Question
What are androgens? These are generally referred to as  male hormones They stimulate or control the  development and mai...
Relationships betweenhormones
Androgens   Testosterone, dehydroepiandrosterone sulfate    (DHEAS), dehydroepiandrosterone    (DHEA), androstenedione, a...
Figure 1 Schematic overview of the generation of androgen precursors and their conversion                               to...
Effect of androgens   Fat deposition (small breast)     Androgens inhibit the ability of some fat      cells to store li...
Effects of androgens on skin   Pilosebaceous unit (PSU)      Androgens cause excess sebum secretion.      Lesions of th...
Hirsutism Excessive male pattern hair growth  (face, back, chest, abdomen and inner  thighs) Graded with the Ferriman an...
Ferrimen-Gallwey
Facial hair
Overview ofandrogenic effects
Male esutheon        Receding hair lineAcanthosis nigricans     Hirsutism
Why do women haveandrogens?   Androgens have important functions in    women    ◦ Essential in the production of E2 (in o...
VirilizationThe development of exaggerated masculinecharacteristics, usually in women, often as a result ofoverproduction ...
Symptoms of virilization   Symptoms of virilization include    ◦   excess facial and body hair (hirsutism),    ◦   baldne...
CAUSES ANDPATHOPHYSIOLOGY
Hyperandrogenism   Excess of androgens may be caused by:    ◦ primary gonadal disorders    ◦ primary adrenal disorders   ...
PCOS ◦ A primary gonadal disorder   Characterized by multiple small cysts within the    ovary and by excess androgen prod...
Developmental origin of PCOS (adapted from Abbott et al., 2002).           Hum. Reprod. Update 2008;14:293-307© The Author...
Features of PCOS•   Symptoms-    •   Oligomenorrhoea/ammenorhea    •   Excessive hair    •   Infertility    •   May presen...
Ovaries
Other features
Metabolic syndrome
Acanthosis nigricans
Rotterdam criteria 2003   A meeting in Rotterdam crafted compromise    criteria    ◦ Any two features from       Irregul...
Primary adrenal disorders Cushing’s disease Congenital adrenal hyperplasia Adrenocortical neoplasms
Cushing’s disease ◦ Primary hypothalamic-pituitary disease ◦ Oversecretion of ACTH from pituitary ◦ Presence of adenoma or...
Signs of Cushing’s   Hypercortisolism    ◦ central obesity, hyperhidrosis    ◦ buffalo hump, moon face, striae   Hyperan...
Congenital adrenalhyperplasiaDepends on the nature and severity ofthe enzymytic defect. Onset of clinicalsymptoms can occu...
Congenital adrenal   hyperplasia◦ Autosomal recessive deficiency of an enzyme  in the cortisol synthetic pathways.◦ Cortis...
Anterior pituitary              Congenital                                   ACT                                          ...
Adrenocortical neoplasms Adrenocortical neoplasms associated  with symptoms of excess of androgen  are more likely to be ...
Tumours
Androgen secreting tumours May occur at any age. relatively rare. should be suspected when the onset of  androgenic sym...
The goals of lab testing  1            2               3           Other causes           of androgen       Look forDocume...
Lab   Testosterone and Dehydroepiandrosterone    sulphate (DHEAS)    ◦ DHEAS hyperandrogenemia of adrenal origin Serum p...
TVS
Therapy
A 22 year old nulligravid women presents to hergynaecologist because of irregular widely spreadmensesCASE SCENARIO
History1.   What question would like to ask the     patient?
Examination1.   Firstly, what systems would you like     to assess2.   Secondly, what are the specific signs     would you...
Further clues   Menarche was at the age of 14, but she    has rarely had regular cycles. For the    past year she has had...
Summary of causes &diagnosis   PCOS.    ◦ At least two of the following three abnormalities were present:      chronic an...
References   Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: toward a    rational approach. In:...
Manage wisely
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Hyperandrogenism ppt 25.1.2011

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an overview of the causes and diagnosis of hyperandrogenism

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Hyperandrogenism ppt 25.1.2011

  1. 1. Hyperandrogenism and virilizationAssoc Prof Dr Hanifullah Khan Amira, Atiqah, Sufia
  2. 2. Objectives1. Androgen2. Virilization3. Causes and patophysiology4. Sign and symptoms5. Question
  3. 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. 4. Relationships betweenhormones
  5. 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. 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. 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. 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. 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. 10. Ferrimen-Gallwey
  11. 11. Facial hair
  12. 12. Overview ofandrogenic effects
  13. 13. Male esutheon Receding hair lineAcanthosis nigricans Hirsutism
  14. 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. 15. VirilizationThe development of exaggerated masculinecharacteristics, usually in women, often as a result ofoverproduction of androgensSo, if hyperandrogenism becomesextreme, virilization occurs
  16. 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. 17. CAUSES ANDPATHOPHYSIOLOGY
  18. 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. 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. 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. 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. 22. Ovaries
  23. 23. Other features
  24. 24. Metabolic syndrome
  25. 25. Acanthosis nigricans
  26. 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. 27. Primary adrenal disorders Cushing’s disease Congenital adrenal hyperplasia Adrenocortical neoplasms
  28. 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. 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. 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. 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. 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. 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. 34. Tumours
  35. 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. 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. 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. 38. TVS
  39. 39. Therapy
  40. 40. A 22 year old nulligravid women presents to hergynaecologist because of irregular widely spreadmensesCASE SCENARIO
  41. 41. History1. What question would like to ask the patient?
  42. 42. Examination1. Firstly, what systems would you like to assess2. Secondly, what are the specific signs would you like to elicit?
  43. 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. 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. 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. 46. Manage wisely
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