In this post, we are going to examine the Excessive Hair Growth And Infertility clinical.. pathology case study no 13. A complete patient history will be presented and you need to guess what is the actual disease behind Excessive Hair Growth And Infertility.
A 22-year-old woman visits her GP because she is embarrassed by “excessive hair growth” on her upper lip, lower abdomen, and thighs. She has waxed her legs and body and shaved her upper lips weekly throughout her teens. In direct questioning of her, she confesses that her periods are irregular since menarche and that she has difficulties conceiving despite having regular unprotected sex with her partner for the past year. Her family had a history of diabetes and hypertension in her mother and maternal grandfather.
Physical examination reveals a mildly obese woman (body mass index [BMI] 31) with moderate facial acne and confirms hirsuitism (Ferriman–Gallwey score 15). Examination of the genitalia is unremarkable, with a patent outflow tract and no clitoromegaly. Bimanual examination reveals a mobile anteverted uterus.
FBC, U+E: normal
Urine β-hCG: negative
1.Suggest a differential diagnosis of the cause of this woman’s hirsutism.
2. Based on the clinical picture, what is the most likely diagnosis and why? To do
Do you know the etiology of this disease?
3. What other investigations would be helpful in confirming the probable diagnosis?
4. What are the management options to treat this woman’s symptoms and in general?
5. Are there longer-term health problems to consider in this patient?
Medically, hirsuitism refers to excessive terminal hair growth in a male pattern in women. Up to 5% of women of reproductive age are hirsuite, according to the Ferriman–Gallwey scale (which scores hair growth in the most androgen-dependent parts of the body, with a score >7 defined as hirsuite). As sexual hair growth is entirely androgen-dependent, androgen levels and the sensitivity of hair follicles to androgens are the primary factors leading to hirsuitism. However, women with milder hirsuitism may not show elevated androgen levels and have what is known as idiopathic hirsuitism, which accounts for around 50% of cases.
The remainder of cases are associated with hyperandrogenism, the causes of which are
(1) polycystic ovarian syndrome,
(2) adrenogenital syndromes (e.g. nonclassic congenital adrenal hyperplasia),
(3) androgen-secreting tumours,
(4) other causes of hormone overproduction, such as Cushing’s syndrome, and
In this woman, the main presenting complaints of hirsuitism and difficulty conceiving, with probable anovulation, are consistent with a diagnosis of polycystic ovarian syndrome (PCOS). PCOS affects up to 10% of women of reproductive age, and is the underlying factor in around 15–20% of infertility cases.
A diagnosis of PCOS, according to the 2003 Rotterdam PCOS Consensus Group, can be made with two of the following three findings:
(1) clinical or biochemical evidence of androgen excess,
(2) oligo- or anovulation, and
(3) polycystic ovaries on ultrasound.
The clinical findings, in this case, are sufficient to meet the first two of these, allowing a putative diagnosis of PCOS to be made. While the exact pathophysiology of PCOS is unclear, one theory suggests that increased gonadotrophin-releasing hormone (GnRH) pulsing leads to increased luteinising hormone (LH) pulsing, stimulating increased production of androgens by theca cells in the ovary. There is also evidence that women with PCOS have elevated levels of insulin, which is known to act synergistically with LH to enhance androgen production by theca cells. Further, insulin inhibits synthesis of sex-hormone-binding globulin (SHBG) by the liver, thereby increasing the proportion of free testosterone in the blood. These effects of insulin account for the hyperandrogenaemia in PCOS, which disrupts the normal follicular development process, leading to anovulation. Before a diagnosis of PCOS can confidently be made, other conditions that produce hyperandrogenism and irregular menstrual cycles need to be excluded.
Further investigations that may be performed to look for other causes include:
- Thyroid function (hypothyroidism)
- Serum prolactin (hyperprolactinaemia)
- 24-hr urinary cortisol (Cushing’s syndrome)
- Morning 17-hydroxyprogesterone levels (elevated in nonclassic congenital adrenal hyperplasia)
- Oral glucose tolerance test and growth hormone suppression (acromegaly)
- Follicle-stimulating hormone (FSH) and oestradiol (high and low/normal, respectively, in premature ovarian failure) Biochemical investigations may show increased testosterone levels, reduced SHBG, increased LH and a high LH:FSH ratio.
An ovarian ultrasound should be performed to visualize the ovaries. Management of PCOS is essentially symptomatic. Hirsuitism and acne are managed by agents designed to inhibit hyperandrogenism, such as the combined oral contraceptive pill, anti-androgens (such as cyproterone acetate or spironolactone), and eflornithine hydrochloride, as well as laser or electrolysis for hair removal. The presence of chronic anovulation carries a higher risk of endometrial hyperplasia and carcinoma, and therefore requires treatment (typically with the contraceptive pill or cyclical progestagens).
Ovulation may be induced with the use of clomiphene (an oestrogen receptor antagonist at the hypothalamus). PCOS also carries a significant risk for the development of metabolic and cardiovascular disease, including obesity, impaired glucose tolerance and diabetes, and accelerated atherosclerosis. The likely pathophysiology behind these is insulin resistance since women with PCOS are usually hyperinsulinaemic. These longer-term complications require similar management to type 2 diabetes, with weight reduction and certain anti-diabetic agents (metformin and the thiazolidinediones) forming the mainstay of treatment.
- Hirsuitism refers to the excessive growth of hair (in a male pattern) in women.
- It may arise from elevated androgen levels or be idiopathic.
- Polycystic ovarian syndrome is a clinical diagnosis that often presents with hirsuitism and oligo- or amenorrhoea.
- The mechanism of hyperandrogenism in PCOS is unclear but may relate to increased GnRH and LH pulsing.
Reference Book: 100 cases in Clinical pathology
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