Elevated IGF-1, Partially Suppressible Hgh, ? Acromegaly


Question

I have a 35 year old female patient complaining of fatigue, night-sweats, joint pains. Was on the b-HCG diet four month ago, has been off that drug for the past 2 months (and has regained all her weight). BMI = 27. Her only other past medical history is of a nontoxic thyroid nodule, herniated disk in 1991, and rheumatoid arthritis for which she takes Lyrica. Complaining of hirsutism on the face (which she lasers.) Has menses monthly although the character has changed.

IGF-1 was measured several times and has been elevated between 350 - 450 ng/mL (about 2 - 2.5 times normal). Prolactin, TSH, FSH, LH normal. I sent for a 75 gram OGTT.

GH at time 0 = 1.3 ng/mL

GH at 1 hour = 6.2 ng/mL

GH at 2 hours = 0.9 ng/mL

GH DID supress to less that 1.0 at two hours, but after a paradoxal climb to 6.2? And, the assay for GH was the newer ICMA...some authorities suggest that with the newer assay GH should suppress to > 0.3 ng/mL, but I'm not seeing that in any guidelines yet.

Pituitary MRI shows a 5 mm microadenoma.

Do you send her to the neurosurgeon? Is the suggestion that GH should suppress to less that 0.3 ng/mL using ICMA in normal practice yet? Patient is anxious and wants something done, she's convinced she has Acromegaly.

Response

I think there are several issues here which might complicate matters:

  1. The new generation monoclonal antibody assays are all subject to interference by circulating antibodies and it is possible that Lyrica is also causing a false positive elevation of GH or IGF-I. If possible, I would suggest discontinuing this for 6-8 weeks and reassaying.
  2. When faced with discrepant results, it is often advisable to repeat the assays using a different laboratory with a different assay, to determine if the same pattern of results is obtained.
  3. Regardless of this, I would expect the GH levels to become completely suppressed in a GTT , certainly to less than 0.5ng/ml. A level of 0.9 ng/ml should be regarded as failure of complete suppression and subject to the IGF-I remaining elevated using a different assay, would support the diagnosis of acromegaly. You have supportive biochemistry, MRI and clinical findings.
  4. However, before submitting to TSS, one could consider a trial of a somatostatin analogue to assess clinical response and any improvement in her symptoms. This would help alleviate any patient concerns regarding ‘something’ being done.

    Paul Jenkins, MD

Possible Treatment of Heterotopic Ossification


Question

The patient is a 65 year-old male with h/o stage II adenocarcinoma of the colon who underwent partial colectomy 3/2010. The surgery was uneventful. His post-operative course has been complicated by heterotopic ossification in the midline incision. The ossification was first noted approximately 4 months after the surgery and CT scan of the abdomen demonstrated an area of heterotopic ossification within the scar tissue starting just inferior to the xyphoid process an dextending 12 cm inferiorly. The abnormal bone is slightly tender to palpation but is causing no significant symptoms other than generalized distress regarding its presence. The patient has no other metabolic abnormalities. Calcium level is normal, kidney function normal. He takes no medications.

The key findings from my review of the literature are that the cause of heterotopic ossification is unclear, removal of the abnormal bone prior to bone maturation might lead to a higher risk of recurrence, that there may be a benefit to prophylactic use of NSAIDs just after excisional sugery to try to reduce that risk, and that there is no clear role for bisphosphonates in this setting.

I'm wondering if there are any experts who might comment on this condition, and if there are any other suggestions for timing/indications for surgical resection and prophylaxis to prevent recurrence. Joyce Leary, MD

Response

You have done an excellent review of the literature. Other than removing the heterotopic bone there is no proven and safe way to treat the problem. I also think prophylactic treatments to prevent recurrence are unproven and radiation is potentially dangerous. NSAIDs would be reasonably safe in trying to prevent recurrence after surgery but there is little evidence of efficacy. Frederick R. Singer, M.D.

Hyperalsosteronism- Adrenal / Renal Vein Sampling


Question

I have a patient with a 1.2 right adrenal mass, hypertension and hypokalemia. Chemistries were consistent with a diagnosis of primary hyperaldosteronism and I had radiology do AVS. The results are puzzling to me:

Left adrenal Left renal Right adrenal Right renal IVC
PRA: 0.12 0.25 0.1 0.92 0.22
Aldo: 204 50 36 42 45
Cort: 15.1 3 3.3 2.8 3.4
Aldo/Cort: 13.5 16.7 10.9 15 13.2

It appears that this is a bilateral situation. Is that your reading? The mass is again on the right but must be an “incidentaloma” Thank you for your help. Ann Ward

Response

Thank you for your case and your thoughtful questions. From the information you have provided, we gather that your patient presented with hypertension, hypokalemia, and a 1.2 cm right adrenal mass on CT scan. There was biochemical evidence of primary hyperaldosteronism, although we do not have the primary data. The patient underwent AVS. From the information provided, it looks as though ACTH was not used in the sampling protocol. The data generated from the procedure are listed above.:

If ACTH is not used during AVS, a side-to-side ratio of more than 2:1 (comparing cortisol-corrected aldosterone ratios) is considered consistent with unilateral disease. This is clearly not the case in the numbers you have provided, so we agree that these data are most consistent with bilateral disease. However, we note that the right adrenal sample looks very similar biochemically to the right renal sample, and so the right adrenal may not have been successfully cannulated (sometimes the radiologist who performed the procedure can tell you if it was technically challenging). But given that there is also no evidence of suppression of the contralateral (left) adrenal (the left cortisol-corrected aldosterone ratio compared to the IVC is about 1), this also supports the lack of unilateral disease.

As you know, non-functioning adrenal ‘incidentalomas’ are not rare, especially in patients above the age of 40 . We know that adrenal anatomy determined by CT scanning may wrongly predict etiology (or lateralization) of hyperaldosteronism in a significant proportion of patients, and that may be the case here from the information you have presented us.

We hope this is helpful in the management of your case. Florencia Halperin, MD, Erik K. Alexander, MD, Robert D. Dluhy, MD