Marked Drop in Bone Density in One Area


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

Short Stature and Hypocalcuria


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

Elevated Prolactin and Tiny ? Tumor


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

Management of Acromegaly


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


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, M D

Probable Hypopituitarism in an Infant


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. R epeat 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.,