Hirsuitism

•     Hirsutism- Tips & Tricks in establishing the etiology of hirsutism.

•     A) What are the phases of NORMAL HAIR GROWTH:-- There are  three classical phases of hair growth- e.g.  Anagen-growth phase; Telogen-resting phase. Catagen- the involution phase.

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•      B) Prevalence of hirsutism is 5-10% of all reproductive age women. Of  all hirsute 57-82% are due to PCOS amongst reproductive aged women &   the other way round  prevalence of abnormal hair growth in PCO is  about 6-10%.

•      In PCOS both ovarian and adrenal androgen contributes in the causation of excessive growth of terminal hairs as is usually seen in males. Hair growth(growth of terminal hairs)  in some  areas of body is considered as abnormal for a woman.

•     C) What are Vellus hairs as is observed in  some areas of body in both men &women .These are fine, no pigmented, short hairs normally present in the healthy female too    ?? These vellus   hairs  responds to circulating androgens very poorly (virtually insensitive) but capable of resending only when serum Testosterone is very much raised.   

•     Such areas where seldom if ever pigment hairs are  seen in women are   Truncal    area of body, particularly back of trunk. The moment a  clinician  see  presence of dark, thick pigmented nonvellus hairs then the immediate diag in woman is “Abnormal Hair Growth” due to androgen excess diosrder  and can’t be due to familial or of PCO origin.  These sites Chest , more importantly back of scapular region , midline  trunk) allow growth of Terminal, black, coarse hairs    only in presence of high dose of androgens.

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•      What are the androgen dependent areas of the body?  Ans:-Upper lip, thighs ,legs, forearms, Chin, mid abdomen , front of chest, and back in that order – the last three sites  are the sites where  if hair is visible then it is unlikely to be familial  and through evaluation is mandatory. Which area of body responds to only high dose of androgens and therefore mandates thorough investigation? Back of trunk & scapular region, gluteal region.

•     D) Where does androgen works? Androgen effects on hair vary in relation to specific regions of the body surface. Hair that shows no androgen dependence includes lanugo, eyebrows, and eyelashes. Excessive hairs present in these areas, therefore mandate no investigation

•     E) Which are the body sites where hair growth should be considered abnormal? Back of trunk, Scapular region & Moustache.

•     What about  hairs located at Beard region ,  Infra-mammary area. Inner thighs. Midline  lower back,. Ans:-In these sites , Vellus hair ( fine, no pigmented, short hairs normally present in the healthy female too)à is converted to  Coarse, Stiff, Pigmented and long hairs  àcalled Terminal hair, only if androgen level is high  and or 5a-reeducates is high locally.

•     G) Etiological Diagnosis of Hirsutism: - The diagnoses of Hirsutism are like a diagnosis of PCOS.

•     By exclusion of different diseases, at least 5 common and 5 uncommon diseases/syndromes have to be excluded by different tests.

•     But majority start treatment with serum Testosterone and DHEASO4 tests only.

•     I) am presence of hirsutism is associated with menstrual disorders/ Weight IN Oligomeno /infertility: - When hirsutism is accompanied by absent or abnormal menstrual periods, assessment of prolactin and thyroid-stimulating hormone (TSH) values is required to diagnose an ovulatory disorder.

•     H) Excess Androgen causes:-evidence of Virilizism/, Clitoromegaly, Clitoral index or muscle wasting or Acanthosis Nigricans (which usually speaks of IIR & Metabolic Syndrome) and Striae in abdomen.

•     I):-Is hirsutism associated with any Metabolic Markers? If there is evidence of overweight/ frank obesity, Acanthosis, increased Waist/ Hip circumference then one should consider assessment of metabolic parameters  (indices of glucose metabolism combined with lipid profile) was offered to all such suspected cases to confirm or refute the diagnosis of PCOS.

•     J):-Associated with subfertility problem? Hirsutism is an incidental finding? Hypothyroidism and hyperprolactinemia may result in reduced levels of SHBG and may increase the fraction of unbound testosterone levels, occasionally resulting in hirsutism as an incidental finding.

•     Therefore, estimation of TSH & PRL (pooled sample) is essential part of initial endocrine evaluation of hirsute cases.

•     K) Correlation with serum Testosterone:-Total Testosterone > 200 ng.
/ml à Adrenal Tumours. Total testosterone:-

•     A) 80-150 ng/dl= PCOS, Hyperthecosis or > HAIR-A Syndrome.

•     B) Total Testosterone: > 200= Cushing's syndrome.

•     But:-Estimation of Total T has limited value unless there is gross virilization. The reason is that the disease which has caused raised production of T may also quantitatively modify the SHBG production. Total Tester one  estimation, therefore without‘

•     Estimating “a) AT- Albumin – bound to Testosterone and b) SHBG may be    less informative. In clinically presumptive hyperandrogenic states (where increased production of Testosterone from any source –e.g. Ovary, Adrenal, Adipose tissue) is not parallel   reflected in serum Tees.  The way/methodology by which we commonly assay. Paradoxically in most cases where hyperandrogenemia is suspected clinically, result come as normal serum Total Tees. Due to concomitant alteration of SHBG level. In my opinion at least 10% of all IVF failure is due to adrenal hyperandrogenism which is only partly taken care by down regulation.

•     How best to diagnose Androgen Secreting Adrenocortical Tumours? This line of investigation has to be considered when the androgen excess reaches the point of virilization. To put in biochemical terms àthe free T in such cases should be >6.85 pg/ml (i.e. 23.6 p mol/Lit) à then follow up with 11-desoxy-cortisol which will be > 7 ng/ml & DHEAS > 3.6 mcg/ml. A 24 urinary cortisol in such cases will usually be > 45 mcg/day.

•     How best to diagnose Congenital Adrenal Hyperplasia? Elevated 17-hydroxyprogesterone (17-OHP) levels identify patients who may have AOAH, found in 1% to 5% of hirsute women. The 17-OHP levels can vary significantly within the menstrual cycle, increasing in the periovulatory period and luteal phase, and may be modestly elevated in PCOS. Standardized testing requires early morning testing during the follicular phase .How best to diagnose CAH? According to the Endocrine Society clinical guideline, patients with morning follicular phase 17-OHP levels of less than 300 ng/dL (10 nmol/L) are likely unaffected .When levels are greater than 300 ng/dL but less than 10,000 ng/dL (300 nmol/L), ACTH testing should be performed to distinguish between PCOS and AOAH. Levels greater than 10,000 ng/dL (300 nmol/L) are virtually diagnostic of congenital adrenal hyperplasia.

•     L) How best to - Stepwise endocrine evaluation will save money? Concentrations of LH, FSH, LH/FSH ratio, testosterone, free testosterone, SHBG and insulin in serum were recorded in 32 women with PCOS and in 25 controls. A model including LH/FSH ratio, insulin and testosterone measurements yielded the best goodness of fit for classification of women with and without PCOS in the logistic regression analysis. Only LH/FSH ratio and insulin were retained as significant variables. The diagnostic characteristics of LH/FSH ratio and insulin for PCOS when compared by receiver-operator characteristic analysis were found to be equally effective. By combining these two variables a higher area under curve was obtained. LH/FSH ratio, insulin or the combination of these two can predict the disease probability in women with PCOS.

•     What is F-G Score? A clinical score of hirsutism??

•      If above> 9 (as is in this case) we proceed for 24 Hr. urinary cortisol starlight way. Not only raised FG Score if there are clinical S/S of Cushingoid feature like Moon faces, Plethora, supra clavicular pad of fat. We always proceed for such test at the outset without wasting much time. If Report> 45 mcg/day-then we should better send her to Endocrinology Deptt. and the immediate diag is Cushing’s, -further tests to follow at medicine Deptt.

•     If the F-G Score is   less than 8:- we perform Urine for preg test in initial visit →-Progesterone withdrawal bleed -→on day 3/4/5 of bleed we estimate traditional/conventional tests for hirsutism e.g.  PCOS.AIAH, HAIR-A syndrome profile.

•     What initial Lab Tests? TSH, Prolactin, Androgens (Total and if possible free Testosterone, DHEASO4, 17-OH Progesterone), 24 Hrs. UFC (urinary Free Cortisol), and Pelvic ultrasound. OGTT, Lipid Profile as necessary

•     Routine Tests. 3) PRL, 4) TSH and 5) PP insulin and PP sugar a-2 hr. after 75 gm.of   Glucose load.

•      6) However in case Total testosterone (which has diurnal variations) has been estimated elsewhere and report come as >200ng/ml (200ng/dL) then also one should seriously consider the possibility of OV/Ad tumours.

•     Tests include 1) 17-OH Prog, (to exclude late onset CAH-if report is >250 mcg/dL-)-this test should ideally be carried out early morning, but Lab seldom are ready by this time. 2) DHEASO4( if this >60000 ng/ml then we have to consider adrenal/Ovarian   tumours .

•     F-G Score is   less than 8:--Tests include 1) 17-OH Prog, (to exclude late onset CAH-if report is  positive  if  report  is >250 mcg/dL-)-this test should ideally be carried out  in early  morning, but Lab seldom are ready by this time. 2) DHEASO4( if this >60000 ng/ml then we have to consider adrenal/Ovarian   tumours  . However -in our deptt we include imaging of ovaries and Adrenals if there are such warning values(backed up by coarse hairs at scapular regions, inner thighs and gluteal regions).  Additionally it  is our routine practice to undertake following tests as most of such exceeds of Androgen Excess Disorders  do present with   sec ameno and on careful exam clinicians observed abnormal  pigmented hair growth ..Such tets are routine doe sec ameno like →3) PRL,  4)TSH and  5) PP insulin and PP sugar a-2 hr. after 75 gm. of  Glucose load . ‘

•      However in case Total testosterone (which has diurnal variations) has been estimated elsewhere and report come as >200ng/ml (200ng/dL) then also one should seriously consider the possibility of OV/Ad tumours. and proceed for imaging modalities forthwith without asking repeating the tests. Similarly  if Free Testosterone  is at all estimated elsewhere –we shall be paying due importance only if it is contemplated by   EQUILIBRIUM DIALYSIS METHIOD which is the standard method of estimating Free Testosterone.. If such report is between 10-30 pg/ml it is likely to be PCOS rather than ad/Ov tumours. I understand there are many more indirect methods of assaying free Tees. I wonder why now a day’s Modified F-G Score is not followed in most of OPD sheets/ Prescription pads in Pvt clinics.!-