Hormone tests -Rationality

 

Hormone tets are costly and not always representative true state of affair due to wrong timing related to M cycle also inter Lab variations due to methodology adopted . In spite of all these limitations  there is an urgent need for “Prioritization of endocrine evaluations in cases of PCO”-- seeking fertility or not interested in fertility??

Which hormones to be done first?? There at least 14 hormones acting ion reproductive system and only   a mad man like me will  insist on tests for all 17 hormones at the first visit or prioritize as per phenotype of PCO & and as per  her chief complaint. Be it that may the common hormones that are tested in a given case are (usually on day  3 of cycle) are 1)  PRL, 2) TSH, 3) LH, 4) AMH, 6) DHEASO4, 6) Cortisol , 8) 17 OH prog, 9) FSH, 10) Free testosterone  11)PP insulin/ PP sugar ratio(not validated) 12) day 3 Progesterone if  follicular cyst > 10   mm on day 3 . 13) progesteorone  prior to LH surge (premature luteinization) etc    

Following  are the women :- Clinically suspected PCOS, B) Non-PCOS but oligo or secondary amenorrhoea, C) all anovulation women, D)  woman suffering from Galactorrhoea, E) gross recurrent acne, F) Frontal alopecia, H) Abnormal hair growth (earlier called ->hirsutism) , G) Acanthosis nigricans, more so if there is F/H/O DM –and majority of hormone investigations bestow on H) All  obese women-warrant detailed endocrine evaluation to arrive at a definitive diagnosis. Therefore there are  eight clinical settings(not to be confused with 4 phenotypes) .

When to maximize the total number of hormone investigations:-All elderly PCO aged >28yrs and trying time is > 4 yrs it appears rational to ask for too many hormones to avoid a LPD, Futile cycle, CC/ Letrozole /hMG to avert A) CC/Let resistant cycle B)  failed cycle, C) LUF, D) LPD F) Poor oocyte and above all E) OHSS etc etc  :--Therefore these are  the eight  clinical settings where no compromise on endocrine evaluation: These eight groups of women and women heading for induction of ovulation and unexplained infertility , LUF also mandate detailed but selective endocrine evaluation-though most cannot afford. An experienced astute clinician can select which hormone to test –and other endocrine test at a later date.

Which hormone in PCO to test ?? Ans:- PCOS is a syndrome and many diseases can mimic/present as PCOS. Fertile or not fertile -it is not sufficient to simply stamp a woman as PCOS. Not all PCOS are endocrinologically alike, but general wisdom dictate the treating physician  that she/he  have to find the exact endocrine abnormality in a given case of PCO and select most suitable treatment for her. In fact now nowadays most ART specialists formulate the treatment plan to treat a PCOS on the basis of her hormonal aberration which are not alike in all PCOS.

What are the expected endocrine aberrations observed in PCOS?   Ans: -Broadly speaking there are five possibilities though a fair number may have combined defects:- some are primary and some endocrine aberrations are secondary. For instance some exhibit a) high insulin or b) high androgen levels, c) some exhibit hyperprolactinaemia, d) high DHEASO4 and rarely some may have 5) high cortisol. The clinician cannot ask for testing all the six hormones. Additionally LH, FSH ratio has to be estimated more so in ART programme. AMH, E2 are dropped in initial evaluation. .Admittedly, as mentioned yesterday evening the reports of insulin and Free testosterone are fallacious in most of the time as these are less informative from the Tr aspect of PCO.

Adoles PCO:-Which hormone to tets on priority basis ?? What about Adolescent PCOS ?  In fact adolescent PCOS also mandate diagnosis of exact endocrine disorder for the origin of PCOS and then select appropriate treatment protocol. What is new in Adol PCO? It is now claimed by the researchers that in adolescent PCO are mostly due to Adiponectin-Leptin-Ghrelin-insulin disorder “backed up tyrosine kinase activity disorders. Earlier it was believed that S/S of PCO in adoles PCO was a nascent PCO and physiological reversible hyperandrogenism due to exaggerate response of adrenal at puberty. But current research has shifted from Adrenal storm to last Tyrosine kinase activity.

What hormone test on priority basis who exhibit primarily Oligomenorrhea but also qualifies for PCO??  Ans; many endocrine disorders may be expressed as oligomeno ,thereby clinicians are in trouble to select the which hormone on proirity   basis . In cases of oligomenorrhea there are cause mostly. If she does not want fertility is not an issue, diagnosis by exclusion O subfertile women may be due to following clinical conditions as well. And each disease mandate different treatment protocol for their primary disease and also for treatment of subfertility. Be sure that a young girl who is really a case of primary  ameneo is falsely claiming that she had one to two courses of spont normal cycles now  only having withdrawal bleeding!! This is often untrue.

 Which hormone to prioritize in cases of abnormal hair growth?? (Hirsutism)

Hirsutism: Such clinical conditions which mimic PCOS (oligomenorrheic/ eumenorrhoic) and with without hirsutism mandate endocrine evaluation to arrive at a definitive clinical diagnosis. Such condition are 1) NC-CAH (Nonclassic adrenal hyperplasia), 2) Cushing syndrome, 3) Virilizing ovarian tumour-all presenting with evidence of hyperandrogenism. The other four conditions which usually present as PCOS 4) hypothyroid, 5) hyperprolactinaemia, 6) acromegaly, and 7) premature ovarian failure (Oligomenorrhoea, weight gain, ovarian enlargement) are. Sometimes 8) drug-related hyperandrogenism may report to us. Elicit detailed drug history before much money is spent on hormone testing with an erroneous diagnosis of PCOS of endocrine disorder.

Which hormone to prioritize in cases of thyromegaly or clinically over hypothyroidism In cases of dysthyroidism both TSH and T4 measurements are essential. 

E) Premature Ovarian Failure

Premature Ovarian Failure: - One should insist on endocrine confirmation.

Unnecessary hormone testing in PCO:-By listing & prioritizing of essential hormones in PCO we  can limit the number of testing  of hormones :: It is true that selections of endocrine tests is guided by the personal and then present history. We often miss this and do unnecessary hormone testing like androgen levels and PRL, Cortisol, DHEASO4 in all cases of PCOS who do not need it.

Continuum of symptoms:    To whom to consider that it is classical PCOS? The problem is that all the four features of PCOS are not present in all cases of PCOS and even if present do not express in equal severity. The problem is that symptoms appear as spectrum of symptoms and signs the occurrence which is dissimilar. It is a continuum and we have to add more endocrine tests as clinical signs appear. The usual sequence is Acne/slight hair growthàslight aberrations in M. cyclesàWt gainà

 PCO & clinical suspicion of PRL disorders: The issue of Hyperprolactinaemia. Ans:- Tr plan:- TypeA  cases If two fold rise that will speak of hyperprolactinaemia. In 20-40% of clinically diagnosed PCOS PRL will be slightly raised but to diagnose that PRL is the primary cause of PCOS (no other endocrine disorder) - then there should be at least two fold rise of PRL. This is due to hyperoestrinismà activation of Lactotrophsà more release of PRLà mastodynia, tenderness of breasts and bloating.

Type B cases:-If less than double level-do not treat by dopamine agonist. Better treat by Insulin sensitizers if unmarried and by OCP if married and does not seek for restoration of fertility.

A)              Clinically suspected PCO : rarely CAH may present in disguise as Late onset CAH !!!:-Role of estimating 17 hydroxyl progesterone.

This is a screening test for CAH (adult onset type) which is also called as NCAH-non classic Adrenal Hyperplasia. The sample should be drawn in early follicular phase and the result should be normally. But pl do remember that  Stress and Female Subfertility...

DHEASO4 When top order for  ?? Causes of elevated DHEASO4 1) attenuated adrenal enzyme deficiency- proved by ACTH stimulation test; 2) Cushing syndrome &  3) Adrenal Tumours are uncommon causes of raised DHEASO4,

In cases of documented NC-CAH & also in cases where there has been repeated anovulation inspite of CC- then administration of dexamethasone will increase the adrenal pool of androgens.In some cases it will improve the ovulation rate. But after one month of initiation of dexa- morning cortisol should be done to assess the degree of suppression of endogenous cortisol by exogenous Dexa. If cortisol is< 3 mcg./mlàthen the dose of Dexa should be decreased. It is not used in pregnancy, Phenotypic analysis helps us to select which hormones to test-i.e. test by exclusion.

 Continuum of symptoms of PCo :    To whom to consider that it is classical PCOS? The problem is that all the four features of PCOS(like A)  Acne/slight hair growthà B) oligomeno  C) Wt gainàD) Anovulation)   are not present in all cases of PCOS and even if present do not express in equal severity. To make the issue more complicated symptoms don’t appear as spectrum of symptoms and signs the occurrence which is dissimilar. It is a continuum and we have to add more endocrine tests as clinical signs appear. The usual sequence is Acne/slight hair growthàslight aberrations in M. cyclesàWt gainà But if a girl was born in mother who had PCOS, hyperandrogenism, dyslipidaemia, & now that mother are diabetic then there is a reason to believe that this adolescent girl is suffering from adolescent Classical PCOS.A low birth weight, premature puberache (appearance of pubic hairs before the age of 8 years.)-need much vigilance for onward development of PCOS.

A)              Adoles. PCOS  either there is Adiponectin-Leptin-Ghrelin-insulin disorder “

tyrosine kinase activity disorders Puberache is an expression of premature activation of Hypothalamo-Pituitary-Adrenal axis.