Possible Adrenal Insufficiency


Question

A 35 year old female presented to a doctor with fatigue, tiredness for few days.She gives h/o that she had used steroid ointment for skin problem for few months. Initial reports showing Cortisol-Morning-125 nmol/L (171-536) and Cortisol -evening-82 nmol/L (64-327). Repeated reports showing Cortisol-Morning-107.9nmol/L (171-536),Cortisol -evening-74.5 nmol/L (64-327) and ACTH-4.8pmol/L (0-10pmol/L),Na+-138meq, K-3.7meq, Cl-105meq, Bicorbonate-26meq,T3,T4 and TSH -Normal. After all these reports, the doctor started her on Prednisolone medications. Later after 10 days, the patient had gone to Endocrinologist, who stopped all tablets and given her dexamethasone for 1 week and done Synathen test-Cortisol; total 5.25 ug/dl (4 to 27) 1hour after synacthen test. Currently she is on Hisone (Hydrocortisone) 10mg 1---1/2 which was reduced to 10mg morning ----2.5 mg evening. I have some doubts about this case:1) Is this a case of secondary adrenal failure? 2) Chance of recovery in these patients? 3) How long patient need to continue this Hisone?4) Is it necessary to repeat Synacthen test after 3 months? 5) Is it necessy to reduce dose gradually over what period? 6) Currently she has hair fall, gaining weight and visceral obesity.with regards.Dr Sreenivas

Response

This patient has adrenal insufficiency probably secondary to adrenal suppression from her medication. She should be taking hudrocortisone replacement until her ACTH stim test normalizes. Try in 3 months . No need for weaning. No need for dex before the test. Just do the test before the morning dose of hydrocortisone. George Chrousos, MD

13 Year Old with Ovarian and Thyroid Dysfunction


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


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.