ENDOTEXT---ASK AN EXPERT The aut

The Authors and Editors of WWW.ENDOTEXT.ORG will attempt to answer questions from physicians about diagnosis and management of endocrine problems. Physicians who wish to submit questions should provide information identifying their place of practice. Responses will be sent by return Email, and questions with general application will be published in this column. Names of correspondents will be included unless we are specifically requested not to do so. Questions may be addressed to any author or editor, and sent to ldegroot@earthlink.net

STATIN TREATMENT FOR ATHEROSCLEROSIS IN THE ELDERLY 20 May 2008
QUESTION- I have a lipid problem that I would be grateful for your
consultant's opinion on. I saw her originally in 1984 with Graves' hyperthyroidism and treated her with 10.6 mCi of I131, after which, she became   hypothyroid and has since then been on an appropriate dose of Thyroxine. She is completely asymptomatic at the present time, and there are no abnormal findings on physical examination. She is a nonsmoker, and on March 28, 2008, her blood pressure was 120/70 mm Hg.
Her mother died at age 91 of a stroke. She has ten siblings,  >> neither of whom has ischemic heart disease.
On February 1, 2008, she had a total cholesterol of 4.61 mmol/L (4 - 5.2 mmol/L), triglycerides 1.55 mmol/L (0.40 - 1.9 mmol/L), HDL   cholesterol 1.52 mmol/L (0.9 - 2.0 mmol/L), LDL Cholesterol 2.39 mmol/L (1.68 - 3.4 mmol/L), and cholesterol/HDL ratio 3.03 (0 - 4). Her Apo-B is low at 0.68 g/L. Her fasting blood glucose is 4.5 mmol/L and other routine blood   work is normal.
Sonographic evaluation of the abdominal aorta shows no evidence of aneurysm. There is mild atheromatous change with early   calcification in the distal abdominal aorta.
On chest X-ray, there is evidence of calcification in the aortic arch.
Echocardiogram shows mild aortic valve sclerosis with minimal   stenosis and mild aortic insufficiency.
Bilateral cerebrovascular duplex scan of the carotid arteries shows a small amount of heterogeneous plaque in the bulb and bifurcation.   There is no evidence of flow restriction or
turbulent flow. There   is no evidence of stenosis.
Two of our cardiologists, on the basis of these findings of early   plaque formation in the carotid arteries, have advised her to have statin therapy and daily Aspirin therapy. They have referred me to   the Canadian Cardiovascular Society Position Statement for the    Diagnosis and Treatment of Dyslipidemia and Prevention of   Cardiovascular Disease published in September 2006 in the Canadian Journal of Cardiology, Volume 22, Number 11, Page 913.
On page 920 the statement is made, "Although intimal medial   thickness quantification is not yet a standard measure, evidence of early carotid atherosclerosis by routine carotid ultrasonography is   an indication for statin therapy."
I would be grateful if your consultant could express an opinion as to the validity of these recommendations. Yours sincerely, D. W. Ingram, MB, FRCPC, FACP
RESPONSE- The question raised by Dr Ingram is very interesting and of course
there is no straight answer to it. In summary, his patient is a
healthy 71 year old woman with no family history of cardiovascular
disease and with no cardiovascular risk factors who was found to have
aortic arch calcifications and carotid plaques. The question is
whether statin therapy should be initiated or not. To make matters
more complicated, her LDL cholesterol is below the NCEP target level
for all dyslipidemia patients with the exception of those at "very
high risk" (documented coronary artery disease AND diabetes or
uncontrolled risk factors).

No clinical endpoint cholesterol lowering study has ever enrolled a
patient with these characteristics, therefore an evidence based answer
can not be directly provided. Most family physicians faced with such
findings on a routine physical examination would probably not
recommend statin therapy. Cardiologists who are usually consulted
because of patient concern will respond to it by recommending statin
therapy on the grounds that the risk of such therapy is low and
statins have been shown to decrease cardiovascular risk in most
situations. A third solution which I would favor is to make
recommendations for additional testing which might enable an evidence
based answer.

1. The mere presence of aortic calcifications is a qualitative rather
than a quantitative result. The quantitative approach to this finding
is electron bean computer tomography (EBCT). This test is relatively
affordable and considered an acceptable method of evaluation of the
atherosclerosis burden. It determines the amount of calcium deposited
on the coronary arteries and it is graded according to age adjusted
standards. There is evidence that its results provide information
concerning cardiovascular risk prediction which is additive to
Framingham risk factors. The finding of a high coronary calcium score
in this patient would justify a therapeutic approach equivalent to
that reserved to a patient with higher levels of traditional risk
factors. To note is that five different studies have showed that
statins do not prevent the progression of calcifications and
consequently the method could be used for the evaluation of risk but
not for the evaluation of the results of therapy.
2. The mere presence of carotid plaques is a qualitative rather than a
quantitative result. Carotid plaques are found at autopsy in North
American children and adolescents. The guidelines quoted by Dr Ingram
are probably referring to a quantitative test, the determination by
ultrasound of carotid intima-media thickness (CIMT). CIMT is
frequently used as a surrogate outcome for interventions aimed at
reducing cardiovascular risk. . There is evidence that its results
provide information concerning cardiovascular risk prediction which is
additive to Framingham risk factors. An estimate of CIMT in this
patient could also refine the evaluation of cardiovascular risk and
justify the intervention.
3. Finally, the estimate of C reactive protein (CRP) is very
inexpensive and could be ordered. CRP level correlates with carotid
plaques and with EBCT. Should it found to be high it could directly
justify the intervention based on the recently completed (but not
published) JUPITER trial. This trial which was stopped because of
overwhelming success enrolled patients with elevated CRP of which a
quarter had LDL cholesterol lower than Dr Ingram 's patient.

I hope this answer will satisfy Dr Ingram. I would be delighted to
add additional information or provide references. DAN STREJA, M.D., FRCPC, FACP.

MANAGEMENT OF RECURRENT ONCOGENIC OSTEOMALACIA-24 APR 2008
QUESTION- I would be most grateful for help with a very difficult problem of oncogenic osteomalacia. The patient is a 62-year-woman who presented to me in 2001 with multiple rib fractures resulting in severe pain. Her serum phosphate was low at 0.56 mmol/L, and she had an undetectable 1,25 Dihydroxy Vitamin D and a low 25 Hydroxy Vitamin D at 29.8 nmol/L. She had an ovoid tumor between the metacarpals in her right hand, and this was removed in March 2002 (unfortunately incompletely removed). This was read at the Armed Forces Institute of Pathology as an atypical fibrochondo-osseous neoplasm of uncertain malignant potential with features suggestive of a phosphaturic mesenchymal tumor (mixed connective tissue variant).
    After this first operation on March 1, 2002, there was remarkable improvement, and by March 27, 2002, the serum phosphate was 1.30 mmol/L and her 1,25 Dihydroxy Vitamin D was normal. At this time she was asymptomatic, and her fractures appear to have healed. Her serum phosphate gradually fell after that, and during 2002 and 2003, it was approximately 0.89 mmol/L – at the lower end of the normal range, but by February 2005, it was low at 0.42 mmo/L. She was being treated, at this time, with Rocaltrol 0.5 µg t.i.d., Calcium Citrate 500 mg t.i.d., and Phosphate Novartis 500 mg q.i.d.
    She had a second operation on August 12, 2004, for the removal of residual tumor, but after this, there was little improvement in the phosphate level. She also had a course of radiation to her hand consisting of 6200 rads in 26 fractions in 2004 and early 2005, but this did not help. Her serum phosphate remained low. In addition, we had been able to send off her FGF-23 to the reference lab in Indiana, and it was high at the beginning and fell back to normal after the first operation. Unfortunately, we have not been able to get it assayed since.On April 5, 2005, she started Octreotide 100 µg t.i.d. subcutaneously, and by June of that year, she was 50% improved in symptoms. Because of expense, this was changed to the long-acting form of Sandostatin LAR 20 mg IM every four weeks. In March 2006, this was increased to Sandostatin LAR 30 mg.
    The phosphate did not normalize after starting the Octreotide; although, her symptoms were somewhat better. At the beginning the tumor was visualized on a Somatostatin scan, and this was true also of the situation before the second operation but since then a Somatostatin scan after being off Sandostatin LAR for a month was negative. Recently her serum phosphate has become very low again, and her symptoms of pain have recurred, and she has multiple fractures again. We are restarting Octreotide 100 mg t.i.d. subcutaneously. I presume that we have either residual tumor in the arm or metastatic tumor, which so far has not been located by imaging investigations.D. W. Ingram, MB, FRCPC, FACP
RESPONSE-Your case is very convincing for a diagnosis of oncogenic osteomalacia. The biochemistry, location, and response to initial therapy are all very typical. The case also presents the difficult management challenges in the disorder. I think you have to assume that there is either residual/recurrent tumor or metastases. I would suggest you try alternate imaging techniques to try and localize this. In addition to octreotide scans, sestamibi and MRI have been used. Most recently the PET scan using CT coregistration has been fruitful and I would suggest this approach. You may also wish to attempt regional venous sampling for FGF23 levels to try and focus the area of concentration of CT scanning, if possible. In addition to the standard therapeutic maneuvers you have tried, another potential therapy could be used (radiofrequency ablation) if the tumor is in a difficult location (see Hesse E et al, NEJM 357: 422, 2007).Thomas Carpenter, MD

IS GROWTH HORMONE THERAPY SAFE WITH RESIDUAL PITUITARY TUMOR? 4 Apr 08
QUESTION- I have a 60 year old patient who is post transsphenoidal resection of a large macroadenoma. He has growth hormone deficiency and hypogonadism and I am weaning him off of steroids. He is much better symptomatically on growth hormone, but a post-op MRI reveals
some residual tumor. Is growth hormone contraindicated here because of the residual tumor? Thank you very much. Ann Ward>
RESPONSE- This is an interesting question. There are two parts to this: firstly, the value of replacing GH in an older age group, and secondly, its safety when there is residual tumour. The answer to both is positive. There is published evidence that GH replacement should be considered regardless of age, although of course the normal range in which one would like to get circulating IGF-1 falls with age; we try and place the IGF-1 in the normal age- and sex-adjusted range but above the median. In terms of safety, there have now been numerous reports which can reference if you are interested in which GH has been shown not to be a risk factor for tumour regrowth or recurrence. However, you should bear in mind that when there is residual tumour postoperativey, the 10-year recurrence rate is pretty high in the absence of external beam radiotherapy regardless as to whether GH is administered. Regards, Ashley Grossman, MD

ALPHA SUBUNITS IN RENAL FAILURE February 26, 2008
QUESTION-Are apha subunit results elevated in premenopausal women with renal failure?Thank you for your reply.Dr MG Endocrinologist, Australia
RESPONSE-They are extremely elevated since they come from hypersecretion of both gonadotropins as well as from already elevated alpha-subunit concentration that are usually found in renal failure. Paolo Beck-Peccoz, M.D.

13 YEAR OLD WITH OVARIAN AND THYROID DYSFUNCTION   18 December 2007
QUESTION- This is a 13 year old Asian girl who came to the clinic with her mother bec of short stature (4ft 4 inches, mother 5ft 2, father 5 ft 8 ). A week prior , they did US of pelvis , reported as possible uterine agenesis.We are doing MRI now to confirm findings. Bone age: 105 months(vs her chronological age of 162 months).difference is >2SD based on the patients age and sex. epiphyseal plates open.
LH 24.01ml/uml, FSH 90.46 ml/uml, estradiol 7 pg/ml tsh irma 18 ;freet4 ria 17;8am cortisol 199.
NO signs of thelarche, no onset yet of secondary sex characteristics.
Will she benifit from GH? Can we immediately start T4? Thanks so much for your input. Lynn Bilar, MD
RESPONSE- Unfortunately, this sounds like a much more complex case than I can handle adequately by e-mail. An initial question is whether or not this patient has Turner syndrome, which would explain the high gonadotropin levels, and short stature, but not the uterine agenesis. She certainly needs a Karyotype done to look not only for XO Turner's but for the rarer variants as well. If, indeed, she has Turner syndrome, then she qualifies for growth hormone therapy and you need do no further testing.
     As far as her thyroid status is concerned, I would want to know why she has an elevated TSH and so would do anti-thyroglobulin Abs, and anti-thyroid peroxidase Abs. I am assuming that the free T4 is in
pmoL/dL and is normal- what is the normal range for your lab? As you may know, there is an increased risk of autoimmune thyroid disease in patients with Turner syndrome. I would see no reason not to treat her for this- it could certainly be contributing to her short stature and delayed bone age.
     Should she have Turner syndrome, then there are many other aspects that need to be explored- cardiac, renal, learning, etc and she needs counselling. Patients with Turner syndrome can die from rupture of an aortic aneurysm, particularly those with undiagnosed coarctation of the aorta. They are also at risk of horseshoe kidney. If she does not have Turner syndrome and she, indeed, has neither a uterus or gonads, she needs renal fx evaluated. She may have a rare genetic abnormality in one
of the transcription factors necessary for genito-urinary development. In either case, it sounds like she needs a sophisticated pediatric endocrine and/or genetic evaluation, and not one that is best handled by
e-mail. I hope that this is helpful to you. I would be most interested in learning about what you find. Rosalind S. Brown MD,

PREMATURE TELARCHE OR PRECOCIOUS PUBERTY 3 December 2007
QUESTION-I am a physician in Romania and I want to ask you about the case of 1 years and 3 months old girl who came in to my office in September 2007. She had breast development on stage 3, noticed by her mother about 6 months. I recommend: estradiol=20pg/ml, FSH=2,4mui/ml, LH=o,o . Because in Romania we don’t have access to LHRH I couldn’t practice THE stimulation test. The skeletal age had no advance And the pelvic ultrasound shows a cyst of 4mm on left ovary. I recommend to avoid food possible contaminated by estrogens and cosmeticals products and ask her to come back after 1 months.
In October 2007 she had no different on her breast, LH=0,1mui/ml, estradiol=80pg/ml, FSH=2,1mui/ml. I found a LHRH agonist (Leuprolid) and I administrated half of 3,75. The basal results were similar with the previous except the estradiol which was again 24 pg/ml. after 1 hour LH=6,7mui/ml, FSH=24mui/ml and after 24 hours LH=7,4 and FSH= 20mui/ml.
How should I interpret the results ? I have an argue with my collaborators about the diagnosis and treatment . So I need your superior opinion to decide what to do next?
RESPONSE-The problem you have been faced with, i.e. the differential diagnosis between precocious puberty and premature telarche in the first 2-3 years of life, is a very controversial one. In this age group, in fact, the hormonal findings are not so helpful in distinguishing between these two clinical entities because both baseline and stimulated gonadotropin and estradiol blood levels can be physiologically increased with values highly variable and inconstant. Therefore, what we should mostly rely on to make a diagnosis, are the clinical findings. In your specific case, there is a 1.5 yr old girl with a 6 months history of breast development, a bone age appropriate for chronologic age, pelvic US showing what presumably is a follicle normally present at this age. It is crucial to know the height velocity in the previous months, and the uterine and ovarian measurements at US. In the presence of a height velocity within normal limits in the previous 6 months, uterine and ovarian measurements appropriate for age, no other signs of pubertal development, and absence of neurological findings, I would go for a diagnosis of premature telarche and follow carefully the patient clinically. In case of precocious puberty I would expect a fast advancement of pubertal signs and ovarian and uterine dimensions, an advanced bone age, and increased height velocity. If this would be the case, I would repeat the GnRh agonist stimulation test and expect to find a further increase in LH and decrease in FSH blood levels, and perform a head MRI to rule out intracranial pathology present in 8% of girls with precocious puberty without neurological findings or neurofibromatosis (Chalumeau, M., et al., Selecting girls with precocious puberty for brain imaging: validation of European evidence-based diagnosis rule. J Pediatr, 2003. 143(4): p. 445-50). Lucia Ghizzoni, M.D.

POLYGLANDULAR AUTOIMMUNITY, HYPOPARATHYROIDISM, AND RESISTANCE TO VITAMIN D THERAPY
QUESTION-I am ibrahim mokhtar endocrinologist working in king khalid hospital , najran , saudi arabia. I have 18 years old female patient . She is a known case with famlial primary hypoparathyroidism and gonadal failure ( APGS ).Her serum calcium was well maintained with one alpha 1 microgram tab.daily and calcium carbonate tab. 1 gram tid . For the last few months it is difficult to maintain her serum calcium . She was admitted to our hospital 10 days back with recurrent carpal spasms .Her serum calcum was low  0.4 mmol and magnisum low 0.5 mmmol , serum albumin is normal . She was treated with I.V CALCIUM GLUCONATE and MG. SULPHATE infusion with symptomatic improvement , however her serum calcium hardly exceeds 1.6 mmol . I increased her dose of one alpha to 2 microgram daily and calcium carbonate t. to 2 g. tid . Upon stopping calcium and magnesium infusion her serum calcium and mag. dropped again with recurrence of carpal spasms . For the last 2 days I am keeping her on calcium (50 ml. cal. gluc. 10% IN 500 ml NS 12 hourly and mag. sulphate ( 3g 12 hourly ) IV infusion. her latest serum cal . is 1.55 mml and mg. is 0.7 mmol . How I can further manage this case. Thank you very much
To Dr. Moktar --One unusual feature of your patient that needs further explanation is the low magnesium, and it would be important to document the degree of hypercalcIuria and hypermagnesuria, as fractional excretions. This should usually be done by 24 hour urines with matching serum that measures calcium, magnesium, and creatinine.
Further information-My patient had familial primary hypoparathyroidism diagnosed about 10 years back with low serum calcium and low serum parathormone level. Her younger sister has the same condition.
(autoimmune polyglandular syndrome) manifested with primary hypoparathyroidism and primary gonadal failure. Her urinary calcium excretion is normal for her body weight and her renal function is normal Her urinary magnesiun not measured , assuming that hypomagnesemia is due to hypoparathyroidism
RESPONSE-Your additional information is very helpful. Has your patient shown any signs or do her laboratory tests suggest any adrenal abnormalities? It would not be uncommon for the exacerbation of the hypoparathyroidism-induced hypocalcemia to be complicated by mild hypoadrenalism.
This would not explain the sudden need for intravenous therapy. In this case, I wonder whether your patient has developed a sprue-like or celiac-related malabsorption syndrome described occasionally in APECED. This would account for the failure of the oral vitamin D metabolite therapy, and has been known to affect oral magnesium absorption.   The key transepithelial transporter for magnesium in gut and kidney is not dependent on PTH for its activity, and hypomagnesemia of the severity you describe is likely due to malabsorption or to a renal leak. In this case, it would be the hypomagnesemia exacerbating the hypoparathyroidism not the converse.
            Before committing to a change in therapy at this point, I would think it important to know that there is no hypermagnesuria when the magnesium is low/normal (between 0.5 and 0.7 mmol/L). Other tests should be directed at establishing adrenal in/sufficiency and ruling out malabsorption. In the meantime, you may require IV support for calcium and magnesium, with aim of maintaining them in the low/normal range (0.6 mM for Mg and enough to stop the Chvostek's ).You may want to consider long-term therapeutic options now: If there is malabsorption, then a celiac type of diet may be effective in the long run. Because magnesium is laxative at doses that overcome its malabsorption, we initiated night-time slow-rate nasogastric infusions to escape the parenteral routes (Cole et al. Eur J Pediatr 2000;159:38). If available you may wish to initiate a trial of recombinant PTH, which we have found to be of benefit in autosomal dominant hypoparathyroidism (see Mittelman et al. J Clin Endocrinol Metab 2006;91:2474).I hope these considerations are helpful. David E. C. Cole MD PhD

PROLACTINEMIA WITH ANTI-PSYCHOTIC MEDS
QUESTION-This case is an 50 year old postmenopausal female who presented with galactorhea and headache. She is also a diabetic on drug control. she is a known case of psychiatric disorder on amitryptiline and sertaline. Her prolactin was 170 ng/ml. Her thyroid function test is normal. No visual field defect. MRI pituitary was normal. our diagnosis was Hyperprolactinemia-Drug induced. But the problem is we were not able to wean her off from the psychiatric medicines and she does not do well with other alternate psychiatric medicine and we are forced to continue the above psychiatric meds. In view of persistant galactorehea and high prolactin, can we go ahead with bromocriptine or cabergoline(with continuation of amitryptiline and sertaline)? Expecting your valuable feedback. Thanking you, Dr.Kumaravel kumaravel velayutham
RESPONSE-Regarding your clinical case, a serum prolactin of 170 ng/mL is an unusual level for aminotryptiline/sertaline induced hyperprolactinemia (was macroprolactinemia excluded?). Generally, drugs which induce such a high prolactin levels are the dopamine antagonist neuroleptic/antipsychotic drugs as sulpiride, haloperidol or chlorpromazine, and, no so commonly, GI drugs as metoclopramide or domperidone. Anyway, if MRI, thyroid and renal function are normal, and galactorrhea is not troublesome for this postmenopausal woman, I would keep the patient on her medication. Otherwise, if galactorrhea is bothering, and the drugs cannot be withdrawal or switched to other medications, I would try a small dose of cabergoline, keeping in mind that in principle the dopaminergic effect of this dopamine agonist may interfere in the anti-depressive effect of the drugs she is taking. Sincerely, Marcello D. Bronstein, MD Sao Paulo, SP, Brazil

Rokitansky-Kuster-Hauser Syndrome (Inadequate Mullerian development) – 12 Jun 2007
QUESTION-I am an endocrinology intern form india,this my second case to the ask the expert section.firstly i would thank u for the advice given for the last case.
The case is 18/F, h/o primary amenorrhoea,Fourth child of a nonconsanguinus marriage,family history- Elder sister had periods at 16 yrs, normal pernatal events,normal developmental milestones,normal intelligence.No history of growth spurt but was growing normally. Thelarche at 12 yrs and pubarche at 14 yrs.No history of virilization at pubertal age.Normal prenatal events.Normal developmental milestones.Normal intelligence. No history of growth spurt but was growing nornally.Thelarche at 12 yrs and pubarche at 14 yrs.No history of virilization at pubertal age.No history of inguinal hernia.H/O infertility in paternal aunt. No history of acne,hirsutism.No history of maternal abortions or neonatal deaths.No history of short stature.
H/o attempted withdrawal to progesterone : no bleeding,. Mother's height: 158 cm. Father is short. Height : 153cm Weight : 48.5kg Height is at 5 th centile.Upper segment : 74 cm Lower segment: 78 cm. Arm span : 153 cm
Thyroid:Normal. Other findings:Smell normal. Pubic hair stage 4, Breast stage 4 Axillary hair has been shaved off.
Local Examination : Labia Majora - normal, labia minora - fused together. Small blind vagianal opening / pouch. P/R - could not get Uterus. Systems :Normal
Investigations: TSH/FT4,PROLACTIN,-NORMAL LEVELS. Testosterone; total 0.097 (ng/ml)(F-< 0.1). FSH-2.43 (mIU/ml)(1-8). LH-<0.1(mIU/ml). Estradiol 154.8 pg/ml. Sonogram of pelvis: Uterus Measures 32.6x8.2mm (CC x AP). Endometrium not visualised. Bilateral ovaries :Not visualised. No obvious pelvic mass seen. : Hypoplastic uterus.No obvious pelvic mass
The question is how to further proceed about the case? any further investigations? management? Arun Kannan:, India <mailto:drarunkannan@gmail.com>
RESPONSE- This 18 year old has genital outflow tract obstruction and perhaps uterine abnormalities and probably represents a variant of Rokitansky-Kuster-Hauser Syndrome.The workup of this patients indicates:
1. Normal progression of pubertal events including thelarche and adrenarche.
2. Adequate growth given the history of short stature in the father.
3. Normal thyroid and prolactin function.
4. Low or normal FSH with ovulatory levels of estradiol.
5. Failure to withdraw bleed with progesterone due to no endometrial compartment.
Thus, this individual has proceeded through puberty, has adequate secondary sex characteristics that are estrogen driven, has a normal XX karyotype but is unable to respond to estrogens due to inadequate development of the Mullerian system and the upper parts of the vagina with a blind vaginal pouch.
To complete her workup, I would probably perform a transrectal ultrasound which may provide further anatomic details such as an absence of a cervix and no endometrium and the presence of ovaries (I disagree that there are absent ovaries since the estradiol levels are too high for peripheral conversion of estradiol).
She can be treated with vaginal dilators to achieve a functional vagina using the approach proposed by Frank.
James H. Liu, M.D. Case School of Medicine, Cleveland, OH

DETECTING OVULATION BY PROGESTERONE LEVEL--- 7 Jun 2007
QUESTION-Traditionally (often a euphemism for "We've always done it though we don't have the evidence") serum progesterone has been used in the UK to assess the likelihood of ovulation having occurred on day 21 of a day 28 day cycle (or 7 days before next period if cycle >28 days). A cut-off of >30 nmol/L ( = 943 ng/dL) is quoted as indicating a likely ovulatory cycle by some. My own response has been that this indicates "evidence of adequate luteal activity".
My understanding of the events leading to ovulation is that an ovarian follicle matures, and that if ovulation occurs, a corpus luteum develops which is responsible for progesterone production. If pregnancy ensues, the placenta takes over. If fertilisation does not occur, the CL regresses and progesterone falls.
I therefore have a question as follows:
If a serum progesterone is measured on day 21, and the result is <30 nmol/L, but, say, in double figures - 10-15 nmol/L - the UK perspcetive in many quarters would be that ovulation had not occurred. However, that being the case, where is the progesterone coming from ? Is it the case that ovulation has occurred but that the ovum is produced, is non-viable with rapid "failure" ensuing, and thus a brief burst of progesterone occurs but which peaks below 30 nmol/L ? Philip Hyde, Pilgrim Hospital, Lincolnshire, United Kingdom
RESPONSEProgesterone is produced from both the adrenal gland and the corpus lutuem. Progesterone production from the adrenal gland is fairly stable and contributes approximately 1-1.5 ng/mL when measured in the serum of women during the follicular phase. Following ovulation, there is increasing production of progesterone from the corpus luteum and the progesterone levels gradually rises from a baseline of 1.5 to 3 ng/mL by the first day after ovulation. Levels then continue to rise until it reaches a peak 7 days after ovulation reaching levels of approximately 10-20 ng/mL. Levels of progesterone are secreted in a pulsatile pattern during the luteal phase and thus levels can vary depending on the timing of the blood draw. (See Filicori et al. J Clin Invest 1984;73(6):1638-47).
In this case, where progesterone is lower than the normal D21 peak probably suggests that the timing of the blood draw was either 3 or 4 days before the peak (i.e. the ovulation was occurring later) or 3 or 4 days after the peak ( i.e. the ovulation was occurring earlier). In the U.S. a level of 4 ng/mL is considered ovulatory. However, the most reliable clinical indicator for ovulation is regular menstrual cycles between 25-35 day intervals. Thus, reproductive endocrinologists seldom measure progesterone levels to confirm ovulation. James H. Liu, M.D. Case School of Medicine

MARKED DROP IN BONE DENSITY IN ONE AREA 20 May 2007
QUESTION-I would like to request an expert opinion on a bone and mineral metabolism case, and ask for your assistance in directing my question to an expert you feel would be most appropriate in addressing this case. 60 year old man with osteoporosis, with unremarkable evaluation for secondary causes of decreased BMD (normal CBC, TSH, testosterone, ESR, PTH/calcium, creatinine, serum protein electrophoresis, 25 OH vit.D), treated with Actonel 35 mg weekly with calcium 1000 mg/day and vit. D 400-800 u/day. Follow-up DXA scan 2 years later showed decrease in BMD of 8% for lumbar spine, and stable proximal femur BMD. Why was there a signficant "disconnect" between lumbar spine and proximal femur BMD on follow up scan, and what would you advise for further diagnostic/therapeutic interventions? Thank you.Bill Jou, M.D.Arcadia, CA
RESPONSE-The most likely explanation here is instrument error, since this much of a disconnect is unusual. If that is not the explanation, then one would need to look harder for an underlying process. You have appropriately excluded significant vitamin D deficiency, hyperparathyroidism, etc. However, if you are convinced that this is not due to some type of instrument error (ie either the initial or f/u spine BMD is erroneous), I would recommend obtaining a bone marrow aspirate and biopsy to be sure there is not an underlying marrow dyscrasia (plasma cell disorder, mast cell disease, etc) that may be causing this. Sundeep Khosla MD,Mayo Clinic College of Medicine

ELEVATED PROLACTIN AND TINY ? TUMOR 12 May 2007
QUESTION-. This is a 27 year old female patient G1P1 who has been having persistent galactorrhea since 2005.She has regular monthly cycles. Her prolactin levels are all normal except for one taken in 2005. Lately she also complains of dizziness and tolerable headaches.MRI done showed a 2-3 mm pit mass.The galactorrhea though very scanty is bothering her. How do we proceed? Thanks a lot again for your time and inputs. Lynn f.w.Bilar.MD
RESPONSE- Regarding your clinical case, certainly the dizziness and headaches are not related to the 2-3 mm pit mass depicted by MRI: more probably the image refers to a pituitary incidentaloma. As most of serum prolactin measurements were normal, probably the patient has normoprolactinemic galactorrhea, a non rare event in women that already delivered and nursed a baby. I suggest to perform prolactin and progesterone measurements at her supposed luteal phase just to assess ovulation. Anyway, if the galactorrhea bothers her (and secondary causes such as dopamine antagonist drugs or hypothyroidism are discarded), I suggest a course of cabergoline treatment. Sincerely, Marcello D. Bronstein, MD

SHORT STATURE AND HYPOCALCURIA 12 May 2007
QUESTION- I would like to ask about non-identical twin sisters, 20 yrs old, with "osteopenia" on DXA. However, their lower Z score (-2,0) is very likely due to their short stature (150 cm). They both have absolute and relative hypocalciuria (1,49 mmol urinary calcium per day, CCa/CCr 0,0048) with normal serum calcium, phosphorus, potassium, magnesium, creatinine, PTH, TSH and 25OH vitamin D levels. The pubertal development was normal and they both have regular menses.
Is there any link between "isolated" hypocalciuria and short stature? What else could be examined in adulthood? Best regards, K. Zajickova Institute of Endocrinology, Prague, Czech republic.
RESPONSE-- I would agree that the small height (4'11") may have a significant impact on the DEXA Z-score. It is somewhat difficult to assess the urinary calcium excretion in this setting. I assume the clearance values are in mmol/mmol. We often normalize 24-hr urine excretion to kg body weight, and I assume that she may also be of a relatively low weight. It would also be of use to know her dietary calcium intake as the value may be accounted for by a relatively low calcium diet. Rare disorders such as Gitelman's syndrome can present with hypocalciuria and decreased bone mass; hypomagnesemia and hypermagnesiuria are usually present. I also assume that such a patient may also be short because of chronic disease, alkalosis, and other electrolyte abnormalities. I am not aware of a specific syndrome of an otherwise healthy child with short stature and low dietary calcium excretion. Tom Carpenter, MD

MANAGEMENT OF ACROMEGALY 10 MAY 2007
QUESTION-I am an Endocrinologist in private practice in Tucson. I was asked to see a patient for hyperthyroidism on Tapazole, he is a 64 year old male. He also has diabetes. When I evaluated him he appeared to be acromegalic, all of his testing confirmed acromegaly, including failure to suppress with glucose. Initial pituitary MRI demonstrated a small left sided pit. micro adenoma, 3x2 mm however when he was ready to undergo surgery he arrested with intubation. He has had 3 subsequent MRI's ,that fail to demonstrate a micro adenoma I suspect that the adenoma involuted. I have evaluated him for ectopic GH secretion with ct scans, octreoscan scan which have been normal. My question is whether I should continue to pursue an ectopic source of GH secretion or treat . I was planning on treating him with Sandostatin Lar. IGF-1 504, IgF Binding protein-3 6.6 TFT wnl. Of interest his IGF-1 level has remained elevated. The neurosurgeon is strongly suggesting pursuing ectopic eval. I was planning on treating him and following the IGF-1 levels. Your help with this case is appreciated, as far as any further testing that I may peruse Thank you very much, M Garcia MD
RESPONSE-thank you for your recent interesting question sent to EndoText. I presume that the GH and IGF-I levels have remained elevated after the initial attempted surgery with failure of suppression of GH after a glucose load, and with detectable GH levels in multiple testingover 12 hour period. If this is the case, it seems unlikely that there has been a spontaneous invlution of the microadenoma asthe biochemistry would indicate on-going active disease.
I would recommend measureing GHRH levels to determine if there is an ectopic source of the hypothalamic hormone. The important issue would be to initiate treatment and to assess the GH and IGF-I response to a somatostatin analogue such as you suggest. I trust you find these suggestions helpful in this interesting case. With kind regards. Paul J Jenkins

LOW PLASMA METANEPHRINE VALUES---STEROIDS, HYPOTENSION- 3 May 2007
QUESTION-I am a practicing clinical endocrinologist. i was asked to see a patient with cns lymphoma who had been treated with high dose steroids and chemotherapy. when the steroids were tapered he developed severe postural hypotension that responded partially to mitodrine and florinef. when steroids were restarted due to cns symptoms without evidence of definite anatomic recurrence of lyphoma the postural hypotension improved significantly. an acth stimulation teat while on steroids showed a normal serum cortisol response. however, plasma metanephrines were below detection limit. can you explain the low metanephrines? George Gewirtz, MD,
RESPONSE- Very interesting. Metanephrines reflect epinephrine secretion from the medulla, and need adrenal cortisol to be methylated from norepinephrine. I suspect there may be pituitary involvement by the lymphoma (we reported a couple of cases in "Pituitary" a few years back) and he is now ACTH deficient (this will not show up acutely in the ACTH stimulation test). If so, he should have replacement therapy with hydrocortisone. In time, I would anticipate the metanephrines will normalise. However, I frequently see patients who are normal with very low urinary catecholamines (we are not currently using metanephrines). Ashley Grossman, MD

PROBABLE HYPOPITUITARISM IN AN INFANT—2 May 2007
QUESTION-I need your help in managing one of my patients.

It was an interesting set up: FT NB baby boy had somewhat complicated delivery, few self -resolved hypoglycemias and was kind of too sleepy/ uninterested in feeding for about 10 days -longer then looked appropriate for the degree of his birth stress, so brain MRI was done. Ectopic small pituitary gland with no visualized pituitary stalk and partial absence of anterior falx were seen. Initial labs at age of 2 weeks showed TSH-5.6, T4 -QNS, LH/FSH <0.2, prolactin 30.1, IGF-1<25, bili 9.2/0.9 (high for 2 weeks), cortisol 1.3.
I was concerned about low cortisol, so ACTH test was done. The samples for 0 and 60' were combined by lab(!!!), so there was no repeat cortisol level at all.I could not r/out panhypopit as well as confirm it for sure, so, as soon as baby was doing better and had no hypoglycemias, he was d/c home with teaching about emergency Solu-Cortef injection and F/up.Meanwhile, abnormal NB screen with low TT4 and normal TSH came, suggestive of central hypothyroidism.Repeat TFT at 3 weeks of age again did not have thyroxin (QNS), and TSH was normal -4.6.
Repeat TFT's showed low FT4 of 0.65 (No TSH in this set because of inability to get enough blood, previous TSH of 4.6 was 3 days ago) Also we found very low Testosterone-7.3, IGF-1 of 17 (mean 55, range 15-109), IGF-BP-3 -1.1 (range 0.7-3.6)
I started this baby on Levoxyl 25 mcg, thinking of possible central hypothyroidism in the light of previous events/findings. Baby was close to 4 weeks old and still had some mild jaundice, supporting my concerns about hypothyroidism.I saw the baby at age of 7 weeks (in 3 weeks after starting Levoxyl) and found well looking active infant boy growing at 90% for Wt and Ht, gaining 700gm (wt-5.4kg) and 4 cm (L-60cm) I repeated TFT's in 3 weeks after starting on Levoxyl 25 mcg: TSH-0.015, FT4-1.69 (0.76-2.00). I wanted the repeat Testosterone to assess the minipuberty, but it was QNS again.
I contacted the mother and while discussing the results, figured out that she thinks that the baby is eating too much and is kind of too active.I decreased the dose to 12.5 mcg, mentioned to her that we will check the levels in 2 weeks. Also I mentioned that I would ask your opinion.
Now are my questions about thyroid aspect of this difficult patient:
Is this an iatrogenic suppression of TSH by too high Levoxyl dose(although it is 5mcg/kg only)? I tend to think so, because we had 3 previous normal levels of TSH before treatment.Or this is a declined function of the thyreotrops of the displaced pituitary?Have no answer for this, as soon as low IGF, low T are suggestive of loss of function. But clinically baby is doing and growing fine, so no data for growth failure and GH deficiency though.
What is my next action if TSH is still suppressed/low and FT4 is still in the high normal? Ignore it or d/c Levoxyl completely?
Does it look like central CH? I would value you opinions and suggestions a lot.I will inform you about future tests and events if you are interested.Thank you so much in advance. Irina Kazachkova, MD, Maimonides Medical Center,
RESPONSE-I think that your patient almost certainly is GH, ACTH and TSH ( and probably LH/FSH) deficient- based on the exceedingly low IGF-1, and low free T4 and random cortisol values. As you know babies with GH (and ACTH) deficiency are at risk of hypoglycemia, but often the blood glucose is only low after fasting, so the fact that you have not documented it does not necessarily rule it out. You need to check a blood sugar prior to the next feed, and be particularly concerned as the baby sleeps longer and longer during the night.
In my opinion, this baby should be started on GH, and cortisol (in addition to T4) ASAP. If it is that difficult to obtain blood and you cannot do either a GH stimulation test (arginine/glucagon) or ACTH test, I would just treat speculatively. Note that with a glucagon stimulation test you can also assess cortisol. With the evidence you have, there is not too much doubt about the dx and many insurance companies will not require formal stimulation tests. I would use a low cortisol replacement dose (<10 mg/kg/day) because of the growth-suppressive effect of cortisol. I would probably use 0.15-2 mg/kg/wk of GH given daily and titrate the dose thereafter according to the growth response, although initially one treats because of the adverse metabolic consequences rather than the growth effects of GH deficiency.
As far as the suppressed TSH is concerned, if the baby is TSH deficient then the TSH is not very helpful in monitoring the adequacy of thyroid hormone replacement and I would follow the free T4. I would not reduce the L-T4 dose (unless the free T4 is elevated using age-appropriate norms).Sincerely,Rosalind S. Brown, M.D.,

HAIR LOSS IN A 30 YEAR OLD, LOW TESTOSTERONE- 26 March 2007
QUESTION-I am an endocrinology intern from Brazil. The case is: Female, 30yrs. She presents with concern for losing hairs and low testosterone, sent by a dermatologist. Menses are normal, no changes in desire or muscle mass or body hair (only alopecia). Hormone profiles: thyroid functions normal , prolactin normal, DHEA normal, LH/FSH/estrogen in normal range. Testosterone = 12,2 (range 15-80) and repeated testosterone=6,9.
The questions: 1) what do I have to think about it (hypothesis)? 2) which are the tests that I have to ask in this case? 3) management? Thanks.A Rubin, Sao Paulo
RESPONSE- First, I cannot offer specific advice in the absence of seeing a specific patient so all I can do is comment about alopecia in general. As you know, most causes of alopecia are not endocrine -- having said that, it clearly can occur as a result of low estrogen (without a concomitant decrease in testosterone) after the menopause. For postmenopausal hair loss estrogen therapy is somewhat effective. Testosterone measurements in laboratories are so poorly performed that I am never confident about any values, low or normal or high. About 25% of testosterone comes from the ovary, 25% from the adrenal, and 50% from peripheral conversion from inactive precursors. So have you considered any adrenal abnormality here? If there is no evidence of this either, I would not think that her hair loss is primarily endocrine. Robert W. Rebar, M.D.

MASCULINIZATION AND HIGH TESTOSTERONE IN A 63 YR OLD WOMAN 24 March 2007
QUESTION-I am an endocrinologist from India. I have an interesting case. I will be happy if you could help me in the management of this case. Case is a 63 year old female, who presented to us with history of hirsutism of 8 years duration and complaints of hair loss in the temperoparietal and frontal area (Male pattern baldness) of 2 years duration.Past issues in this case: 1.She undervent hysterectomy with Bilateral salphingo oopherectomy 8 yeras before (Indication not known). 2.Total thyroidectomy for MNG 1 year before. Now euthyroid on thyroxine replacement.(HPE: MNG, No evidence of malignancy) No history of drug intake or other co-morbidities.On examination she had Hirsutism(FG score>30), masculanizing features and voice change were present. She also had clitoromegaly. No evidence of cushings syndrome.
Investigations:
TSH-3.2mIU/l(0.3 to 4) on thyroxine 150mcg/day
RFT, LFT,Calcium, sodium, potassium-normal
Testosterone-6.14ng/ml
17 hydroxy progesterone-1.3ng/ml
DHEAS-259.2mcg/dl (normal: 80-390)
CT scan Abdomen: Adrenals normal. No abnormal pathology.
MRI of neck and chest to r/o germinoma was normal.
We had treated the patient with aldactone 100mg/day and finasteride� 5mg/day for 3 months and still her testosterone is 5.1ng/ml and not much of clinical improvement.The question of concern is: 1. What is the probable diagnosis and how do we proceed further? 2.How do we treat her? Dr.Kumaravel Amrita Institute of Medical Sciences, Cochin, India
RESPONSE- It is again difficult to address a specific problem in the absence of seeing a specific patient.All I can do is make some general comments.It would appear that the testosterone values are about 10 times the upper limit of the normal range for women. If this is the case, then a source must be identified. Generally speaking, testosterone is produced by ovarian androgen producing tumors (generally benign). These tumors can be quite small. Ovarian tissue can remain in the pelvis even if a BSO is produced. It would be reasonable to search for a source of androgen excess. IF there is a skilled interventional radiologist samples could be obtained from near the origins of the ovarian vessels and from other sites in the abdomen and measured for testosterone. This might help determine if surgery is warranted.It would not be unreasonable to determine if the testosterone is suppressible during a dexamethasone suppression test -- but this can occur with ovarian as opposed to adrenal lesions. Robert W. Rebar, M.D.

HYPOCALCEMIA FOLLOWING THYROID SURGERY  FOR HYPERTHYROIDISM 20 Mar 2007
QUESTION-I have a patient who has had thyroidectomy for Graves 3 weeks back. He was admitted initially with fast AF and high output cardiac failure. He had treatment with high dose PTU, propranolol, Potassium Iodide and Warfarin.He was adequately prepared and proceeded to total thyroidectomy.
      He developed severe hypocalcaemia ( corrected Ca 1.53 mmol/L), and has required continous infusion of Calciem gluconate and 8 gm elemental cacim orally to keep his Calcium around 1.9 mmol/L and symptom free, for 3 weeks post operatively. His Mg initially was low and is now in the normal range on oral Mg replacement. Phosphate has been high between 1.55 to 1.93 mmol/L.. His 24 hour urine Ca with a paired serum Ca of 1.9 mmol/L was low at 2.2mmol/24 hrs (NR 2.5 -7.5). He has been receiving 2 micrograms a day of alpha calcidol.
      It seems as though he has hungry bone syndrome. Serum PTH is awaited. He was non compliant with ATD for about 4 years prior to developing high output heart failure and AF. I am not entirely sure what to do next. Is it just a question of time before his calcium normalises or is there any other modalities of treatment? Dr S.P., England
RESPONSE- While it is always important to avoid coming to premature closure and to fully consider the differential diagnosis of hypocalcemia, in this instance the described clinical situation is classic for surgically-induced hypoparathyroidism. Most likely the parathyroids were inadvertendly removed or traumatized during neck surgery. As such, I would expect the pending PTH level to be low, or inappropriately 'low-normal' in the face of hypocalcemia. Treatment would typically involve calcitriol and calcium, with related issues more fully described in the Endotext chapter. In followup, one should consider the possibility that traumatized parathyroid tissue can sometimes recover function over a period of weeks or months. Andrew Arnold, MD

TREATMENT OF ALOPECIA WITH PROPECIA 9 March 2007
QUESTION-. I am treating a 21 years old male with androgenic alopecia pattern. His hormone profile is normal. For the last 6 months he received Propecia (A selective 5 alpha reductase inhibitor) showing a nice improvement. How long do I have to continue the treatment? What will happen once I stopped the treatment? Shilo, Shmuel M.D
RESPONSE-Androgenetic Alopecia is a chronically progressive condition that occurs in people with an inherited susceptibility and is mediated by the action of androgens and, in particular, dihydrotestosterone in the hair follicle androgen receptor. Blocking the synthesis of dihydrotestosterone will arrest progression of hair loss but will not change the natural history of androgenetic alopecia in people who are genetically pre-disposed. As such, the treatment will continue to arrest the hair loss for as long as the treatment is continued. When the treatment is stopped then the hair loss will resume. In answer to your question, the treatment needs to be continued for as long as he needs to keep his hair. Professor Rodney Sinclair, University of Melbourne

FINAL HEIGHT FOLLOWING “EARLY” PUBERTY? 5 Feb 2007
QUESTION- I am an endocrinology intern from india,the case is a 12yrs 8month old boy
presents with concern for short stature and puberty advancement,(voice broken
at 11yrs, axillary hair 111/2 yrs), when comparing with the peers. ht
145cm/wt38.5,axillary hair stage 3/pubic hair stage 3/testis 20ml on both
sides/phallus length 8cm/bone age 13-14yrs,
Hormone profiles thyroid functions normal , prolactin normal,17OHP
normal,LH/FSH are in pubertal range. sr.testosterone slightly lower than the
normal range.
The question 1) his concern is how tall he will grow? (mother and father ht
152cm/155cm)
2) Is there any way his mild advancement in puberty can be slowed or delayed?
3) management? Dr.Arun Kannan, Amrita Institute of Medical Sciences, Cochin, India
RESPONSE- I believe that your patient had a normal, or sligthly anticipated pubertal
development. Despite a testicular volume of 20cc, his predicted height with
a bone age of 13.5 yrs is 160cm (BA 13: 165 cm; BA 14:156 cm) which is
exactly the same as his target height that is 160 cm. I don't think is worth
doing anything, and I believe that slowing the pubertal process at this
point might either harm his growth pattern by eventually stopping his
pubertal spurt, if he he has not been through it yet, or just be useless. I
would just continue a clinical follow-up reassuring him that he will
probably achieve his father's height. Keep me updated on your patient's follow-up.
Lucia Ghizzoni M.D., Ph.D

AHO, PSEUDOHYPOPARATHYROIDISM, AND BICUSPID AORTIC VALVE 20 Nov 2006
QUESTION- I´m caring for an patient with AHO and Pseudohypoparathyreoidism. Also she
is suffering from aortic stenosis caused by a bicuspid aortic valve. Is there any known linkage between AHO and bicuspid aortic valve ? Sincerely yours, Dr P.Matheiowetz
RESPONSE-Thanks for your query. I recommend you contact Dr. David Cole in Toronto and he would have further insights. Patients with 2q37 deletion have been reported with an Albright hereditary osteodystrophy (AHO)-like phenotype and ductus arteriosus and possible bicuspid aortic valve (see Reddy KS et al 1999 Microdeletion of chromosome sub-band 2q37.3 in two patients with abnormal situs viscerum. Am J Med Genet 84: 460-468 and references therein – see Table 1). Yours sincerely, Geoff Hendy, MD

DIAGNOSING AND MANAGING HYPERNATREMIA 8 Nov 2006
QUESTION-Could you pl write how to differentiate if hypernatremia is from hypo or adypsia versus reset osmostat in an individual with hx of head injury in the past and if the history about thirst is limited because of mental retardation. Also pl let me know how to manage hypernatremia from reset osmostat. padmalatha berikai
RESPONSE- This is a difficult problem, and in principle it may not be possible to differentiate hypodipsia from a reset osmostat (indeed, they may be pathophysiologically the same process). Managing patients with adipsia is one of the most challenging to neuroendocrinologists, and this is especially the case with patients less mentally astute. I generally admit them for a few days and get a baseline weight and fluid intake which keeps the serum osmolality in the normal range, and then instruct their carers to keep them to this input with at least weekly weighing. If their weight departs from the determined set-point then the fluid intake can be adapted accordingly. If possible, a check on the osmolality at intervals will allow them to see if the balance is working out. This means a lot of input from the carer, but the only patients who do well long-term are those with good home input. Ashley Grossman, MD

RELIABILITY OF CORTROSYN TEST 7 Nov 2006
QUESTION-I did a CST on a young male, aged 16, because he had been given some compounded steroids by a "fibromyalgia clinic" because of diagnoses adrenal insufficiency. The early AM cortisol level was low at 2.1 ug/dl and the one hour was normal at 25.9 ug/dl. What is the significance of the low 8 AM value and do I need to do anything else? Clinically, he had hyperthyroidism due to compounded T3 from the same clinic and, of course, the T3 has been discontinued and further evaluation will be done in a few weeks after being off of the T3. Thanks for your help with this. Ann Ward, MD Taylorsville, GA

HYPOGLYCEMIA, PULMONARY AND PERIPHERAL EDEMA 9/17/2006
QUESTION-I am an IM doc in Yuma, AZ. I recently had a patient, 31y/o WF, hospitalized after showing up in the ER semi-comatose, with a glucose of 40 and pulmonary and peripheral edema. Only PMH is depression for which she takes Cymbalta with good results.
Her fasting (12hr) insulin was <2, her pro-insulin <5 and c-peptide was 1.0. Her CMP/CBC/TSH were normal. I thought maybe insulinoma before I drew the labs, and now I'm thoroughly confused. Any ideas? Thank you. RSmythe MD
RESPONSE-Since I do not have much clinical information I will answer this based on several different assumptions.
Assumption 1. The glucose was from a venous sample, not a finger stick. If this patient was in cardiac failure and in a degree of cardiovascular collapse, it is possible that there was peripheral vasoconstriction. When this occurs, it has been shown to lead to a false low glucose level on a finger stick test.
Assumption 2 -The Patient Did Not Have Cardiac Failure
In 2000, Ortega et al in Diabetes care (Ortega et al. 23 (7): 1023. (2000) published their observation of the relationship of hypoglycemia and pulmonary edema. This occurred in a diabetic patient who had a hypoglycemic seizure. In a follow-up letter, Matz (Diabetes Care 23 (11): 1715. (2000)), pointed out a long forgotten association of non cardiac pulmonary edema as a consequence of grandmal seizures.
Thus in this case, given that the finding of hypoglycemia was real (see above), then hypoglycemia and seizure could still be underlying this.
Assumption 3. The Patient Did Have Cardiac Failure
In this case, the cardiovascular issues raised above again must be satisfied. If the glucose level was "real," then one can rarely see severe hypoglycemia with severe hepatic congestion and dysfunction. One always would be concerned about the possibility of ethanol with hypoglycemia and cardiac problems.
So given all the above, where does that leave us. At this point, the data you present does not help. Insulin levels, proinsulin and c-peptide will only help if they are drawn at the time of hypoglycemia. In addition, testing for sulfonylureas would need to be done, with specific request that glimepiride and meglitinides be tested as these are not checked for on the routine screening tests of the past.
Proactive testing at this point can be done with a formal 72 hour fast that would require hospitalization. 99% of patients with an insulinoma will reveal themselves during this time. Other tests, such as a 72 hour continuous glucose monitor can be done, but given the history here, it is unclear if that test would be as helpful.
After these tests, if hypoglycemia is found, the concurrent insulin, c-peptide, proinsulin, and cortisol levels should lead to a correct diagnosis.Robert J. Rushakoff, MD
Note added- Cymbalta has been associated with the “inappropriate ADH syndrome” which might be part of this problem but could not explain it all. What was her serum sodium? L DeG

ESTROGEN THERAPY IN GENDER DYSPHORIA 9/1/2006
QUESTION-I am an endocrinologist in private practice. I have a transgender pt (male to female) who received hormone therapy in Florida, as per the pt. Could you advise me in regards to the dose of E2 the pt is maintained on and what we specifically need to monitor. I understand the mammo should be done but is there anything I need to follow? I would very much appreciate your information. Thank you. Elise Kwon, M.D.
RESPONSE-I have done this for approximately 40-50 individuals. Before starting estrogen treatment, I get a Leiden V and a prothrombin G20210A gene screen. I will usually use a 0.1 mg estradiol transdermal patch which should give a 100-150 pg/mL estradiol level. This will be easy to measure if you want and will detect any cheating or overdosing by the patient. (This group often thinks that more estrogen is better). I also get a psychology consult with a clinician experienced in gender dysphoria evaluation before starting on estrogen therapy. James H. Liu, M.D. .

TESTING FOR ADRENAL INSUFFICIENCY
QUESTION-I am a first year Internal Medicine Resident at Rio de Janeiro, Brazil. In my ward there is a patient with Paracoccidioidomycosis which is a deep mycosis present predominantly in South American countries (around 80% of the cases report described in Brazil). Current recommendations support the screening for adrenal insuficciency in all patients since the adrenal gland is the third organ most involved in this disease. Our patient has severe symptomatic disease in the lungs, oral cavity and larynx but has no symptoms/signs or laboratory evidence of Addison's Disease (electrolyte disturbances, etc). Unfortunately our poor public resources do not allow us to use the high-dose short synacthen test (SST). My question is: in the absence of the SST what is the applicability of the Insulin Tolerance Test in diagnosing subclinical primary adrenal insufficiency or even manifest disease? Is it a valid test? And the other question is: is the low-dose SST a reliable test for the diagnosis of primary adrenal insufficiency or should it be reserved only for diagnosing secondary and tertiary adrenal failure? I have read this topic in a few places and I have not things clear in my mind yet. Andre Faria, MD
RESPONSE-The standard ACTH test is the best. The low dose ACTH would not be helpful. It should be used in research studies looking for subtle changes in adrenal function. The ITT is as good as the standard test but has risks. You might also contact Prof. Ayrton Moreira, University of Riberao Preto, on this topic. Best regards!
Dr George Chrousos

ELEVATED PROLACTIN NON-REPONSIVE TO CABERGOLINE 5 May 2006
QUESTION-I'm an argentine endocinologIst. I have a patient 18 years old young woman. She had her first menstruation at 14 y/o and was regular for 2 years. Then she started a secondary amenorrhea with PRL over 120 ng/ml. She consulted me on September 2005. I didn't find galactorrhea, the weight was normal (BMI 24), the genetic study was normal, the MRI in September showed a normal pituitary gland, except for a very little image suspicious, but not clear. The fractionated PRL was elevated in all the fragments. We start with cabergoline in crescent dose. At the present time, with 4mg of cabergoline, the MRI shows a decrease of pitutary size, PRLis 100 ng/ml and she is still amenorrheic as the only symptom. She shows some sign of emotional stress but refuses psychotherapy. How do I best manage this patient? Thank you for your attention and your advice. Forgive my poor english. Susana Nemas, MD. La Plata. Rep Argentina

RESPONSE-Thank you. This is a difficult problem. The initial prolactin with only a suspicion of a microprolactinoma raises the possibility of macroprolactin
interference in the assay, but I take your point on the 'prolactin fractions' to have excluded this possibility. If not, retesting the current prolactin after polyethylene glycol precipitation may reveal whether this all all monomeric prolactin. If it is, then the dose of cabergoline is already very high, so you could switch to an alternative drug such as quinagolide, although my experiece is that there is usually cross-resistance to all drugs. If the only problem is lack of menstruation then simply starting the oral contaceptive pill will provide regular menses and avoid the risk of osteoporosis, but regular rescanning is mandatory. Alternatively, a new high quality MRI should be discussed with an experienced transsphenoidal surgeon with a view to microadenomectomy. Ashley Grossman, MD