Changes in CVD risk post-parathyroidectomy in PHPT

Effects of successful parathyroidectomy on metabolic cardiovascular risk factors in patients with severe primary hyperparathyroidism. 
Ishay A, Herer P, Luboshitzky R.

[Endocrine Practice, 2011, Ishay, parathyroidectomy, DBP, CVD]

http://www.ncbi.nlm.nih.gov/pubmed/21324826

- study to evaluate effect of parathyroidectomy on metabolic abnormalities associated with CVD

- 34 Pt with HPT and 40 control patients with normal calcium assessed at baseline and 1 year later. HPT patients had parathyroidectomy

- significant decrease in DBP and insulin. significant increase in spine BMD

- no significant change in metabolic syndrome rate, insulin resistance, or likelihood of CVD risk

Two Different Corticosteroid-Binding Globulin Variants that Lack Cortisol-Binding Activity in a Greek Woman

[JCEM, 2012, Hill, SERPINA6, non-functioning CBG, immunoassay]

JCEM 97:4260-4267, 2012

http://jcem.endojournals.org/content/early/2012/08/31/jc.2012-2467.short

• L. A. Hill, D. A. Vassiliadi*, M. Simard, A. Pavlaki, I. Perogamvros, D. Hadjidakis andG. L. Hammond*

- Title: Two Different Corticosteroid-Binding Globulin Variants that Lack Cortisol-Binding Activity in a Greek Woman

- Author: Hill

- JCEM 2012

- SNPs that alter production or function of CBG are rare

- novel heterozygous c. 1282G>C transversion in exon 5 of SERPINA6 resulting in W371S substitution in area which plays key role in anchoring steroid-ligands to binding site

- no measurable CBG activity despite normal CBG level

- immunoassays fail to reflect CBG activity

Thyroidal Effects of Metformin Treatment in Patients with PCOS

(click the title above to get to the paper)

Mario Rotondi et al.

Clin Endocrinol. 2011;75(3):378–381

Objective

Metformin is widely used for the treatment of type 2 diabetes. Growing evidence supports the beneficial effects of metformin also in patients with polycystic ovary syndrome (PCOS). It was recently reported that metformin has a TSH-lowering effect in hypothyroid patients with diabetes being treated with metformin.

Design

Aim of this study was to evaluate the effect of metformin treatment on the thyroid hormone profile in patients with PCOS.

Patients and measurements

Thirty-three patients with PCOS were specifically selected for being either treated with

levothyroxine for a previous diagnosis of hypothyroidism (n = 7), untreated subclinically hypothyroid (n = 2) or euthyroid without levothyroxine treatment (n = 24) before the starting of metformin. The serum levels of TSH and FT4 were measured before and after a 4-month period of metformin therapy.

Results

Thyroid function parameters did not change after starting metformin therapy in euthyroid patients with PCOS. In the 9 hypothyroid patients with PCOS, the basal median serum levels of TSH (3!2 mIU/l, range = 0!4–7!1 mIU/l) significantly (P < 0!05) decreased after a 4-month course of metformin treatment (1!7 mIU/l, range = 0!5–5!2 mIU/l).

No significant change in the serum levels of FT4 was observed in these patients. The TSH-lowering effect of metformin was not related to the administered dose of the drug, which was similar in euthyroid as compared with hypothyroid patients with PCOS (1406 ± 589 vs 1322 ± 402 mg/day, respectively; NS).

Conclusions

These results indicate that metformin treatment has a TSH-lowering effect in hypothyroid patients with PCOS, both treated with l-thyroxine and untreated.

Androgen abuse in athletes

Shehzad Basaria
CLINICAL REVIEW:Androgen Abuse in Athletes: Detection and Consequences
J Clin Endocrinol Metab 2010 95: 1533-1543

I liked this article for several reasons:

1. Interesting and timely topic. Not only as it relates to professional sports, but also office consultations from non-professional athletes who have gotten involved in performance enhancement, knowingly or unknowingly through "supplements".

2. Nice mini-review of androgen synthesis and degradation and how this relates to detection

3. Interesting biochemistry for the assays. I love the genetic engineering of yeast to contain androgen receptors which can then activate the firefly gene luciferase to glow in the presence of androgen. See figure 4 for that.

Naturally you can check out the article as a pdf at Google docs through goodreader. By the way I downloaded Apple's Pages and am looking into a keyboard for the iPad now. This article comparing keyboards was helpful.

Weighing Risks and Benefits of Liraglutide — The FDA's Review of a New Antidiabetic Therapy

Weighing Risks and Benefits of Liraglutide — The FDA's Review of a New Antidiabetic Therapy
Published at www.nejm.org February 17, 2010 (10.1056/NEJMp1001578)

Worthwhile read not only for the interesting potential link between this medication and medullary thyroid cancer, but also a look at what goes into the approval process for new diabetic medications.

Geek stuff

These technologies may someday make their way into medicine and EMR technology. In any case it's just cool stuff.

Thin Film Turns any Surface Into a Touchscreen

Spray-on liquid glass is about to revolutionize almost everything

Lose more weight with bigger breakfast?

Interesting summary of a study presented at Endo Society Meeting by Dr. Daniela Jakubowicz. Also info about a book.

Breakfast of Champions--and thin people

Corned beef for breakfast

18F-DOPA PET provides superior imaging for pheochromocytoma

6-[F-18]Fluoro-L-Dihydroxyphenylalanine Positron Emission Tomography Is Superior to Conventional Imaging with ¹²³I-Metaiodobenzylguanidine Scintigraphy, Computer Tomography, and Magnetic Resonance Imaging in Localizing Tumors Causing Catecholamine Excess.

Helle-Brit Fiebrich, Adrienne H. Brouwers, Michiel N. Kerstens, Milan E. J. Pijl, Ido P. Kema, Johan R. de Jong, Pieter L. Jager, Philip H. Elsinga, Rudi A. J. O. Dierckx, Jacqueline E. van der Wal, Wim J. Sluiter, Elisabeth G. E. de Vries and Thera P. Links.

The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 10 3922-3930

Abstract:
Context: Catecholamine excess is rare, but symptoms may be life threatening.

Objective: The objective of the study was to investigate the sensitivity of 6-[F-18]fluoro-L-dihydroxyphenylalanine positron emission tomography (¹⁸F-DOPA PET), compared with ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy and computer tomography (CT)/magnetic resonance imaging (MRI) for tumor localization in patients with catecholamine excess.

Design and Setting: All consecutive patients with catecholamine excess visiting the University Medical Center Groningen, Groningen, The Netherlands, between March 2003 and January 2008 were eligible.

Patients: Forty-eight patients were included. The final diagnosis was pheochromocytoma in 40, adrenal hyperplasia in two, paraganglioma in two, ganglioneuroma in one, and unknown in three.

Main Outcome Measures: Sensitivities and discordancy between ¹⁸F-DOPA PET, ¹²³I-MIBG, and CT or MRI were analyzed for individual patients and lesions. Metanephrines and 3-methoxytyramine in plasma and urine and uptake of ¹⁸F-DOPA with PET were measured to determine the whole-body metabolic burden and correlated with biochemical tumor activity. The gold standard was a composite reference standard.

Results: ¹⁸F-DOPA PET showed lesions in 43 patients, ¹²³I-MIBG in 31, and CT/MRI in 32. Patient-based sensitivity for ¹⁸F-DOPA PET, ¹²³I-MIBG, and CT/MRI was 90, 65, and 67% (P <> for ¹⁸F-DOPA PET vs. both ¹²³I-MIBG and CT/MRI, P = 1.0 ¹²³I-MIBG vs. CT/MRI). Lesion-based sensitivities were 73, 48, and 44% (P <>18F-DOPA PET vs. both ¹²³I-MIBG and CT/MRI, P = 0.51 ¹²³I-MIBG vs. CT/MRI). The combination of ¹⁸F-DOPA PET with CT/MRI was superior to ¹²³I-MIBG with CT/MRI (93 vs. 76%, P <> ¹⁸F-DOPA PET correlated with plasma normetanephrine (r = 0.82), urinary normetanephrine (r = 0.84), and metanephrine (r = 0.57).

Conclusion: To localize tumors causing catecholamine excess, ¹⁸F-DOPA PET is superior to ¹²³I-MIBG scintigraphy and CT/MRI.

Comments:
Localizing catecholamine secreting tumors can be notably difficult. This study looked at several imaging modalities in 48 patients with known catecholamine excess. Imaging included 18F-DOPA PET, 123I-MIBG, CT, and MRI.

The highest sensitivity for detecting lesions was 18F-DOPA Pet with CT/MRI which had a 94% sensitivity. 18F-DOPA PET alone had a 72% sensitivity. In contrast, 123I-MIBG with CT/MRI had only a 76% sensitivity. CT/MRI alone was noted to miss mainly adrenal lesions less than 2 cm.

The final histology in patients who received surgery was Pheochromocytoma in 40 patients, adrenal hyperplasia in 2, paraganglioma in 2, ganglioneuroma in 1. 3 remained unknown because no lesions were detected.

At least from this report it appears that combination 18F-DOPA with CT or MRI would be the best way to localize tumor mass in patients with catecholamine excess.

Pancreatic fat and diabetes

Noninvasive Quantification of Pancreatic Fat in Humans

The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 10 4070-4076
Ildiko Lingvay, Victoria Esser, Jaime L. Legendre, Angela L. Price, Kristen M. Wertz, Beverley Adams-Huet, Song Zhang, Roger H. Unger and Lidia S. Szczepaniak

Objective: To validate magnetic resonance spectroscopy (MRS) as a tool for non-invasive quantification of pancreatic triglyceride (TG) content and to measure the pancreatic TG content in a diverse human population with a wide range of body mass index (BMI) and glucose control.

Methods: To validate the MRS method, we measured TG content in the pancreatic tissue of 12 lean and 12 fatty ZDF rats (ages 5–14 weeks) both by MRS and the gold standard biochemical assay. We used MRS to measure pancreatic TG content in vivo in 79 human volunteers. Additionally, to assess the reproducibility of the method, in 33 volunteers we obtained duplicate MRS measurements 1–2 weeks apart.

Results: MRS quantifies pancreatic TG content with high reproducibility and concordance to the biochemical measurement (Spearman’s rank correlation coefficient = 0.91). In humans, median pancreatic TG content was as follows: (1) normal weight and normoglycemic group 0.46 f/w%, (2) overweight or obese but normoglycemic group 3.16 f/w%, (3) impaired fasting glucose or impaired glucose tolerance group (BMI matched with group 2) 5.64 f/w%, and (4) untreated type 2 diabetes group (BMI matched with group 2) 5.54 f/w% (Jonckheere-Terpstra trend test across groups p <>

Conclusions: Human pancreatic steatosis, as measured by MRS, increases with BMI and with impaired glycemia. MRS is a quantitative and reproducible non-invasive clinical research tool which will enable systematic studies of the relationship between ectopic fat accumulation in the pancreas and development of type 2 diabetes.



--------------------

Comments:
How is pancreatic fat related to diabetes/IFG and how is it related to fat deposition in other organs? This intriguing study examines both animal models and humans to help understand the pathophysiology of fat deposition and its relationship to diabetes.

The figure above in A. shows glucose readings along with total pancreatic Triglycerides(pTG) as assessed by magnetic resonance spectroscopy. The pancreatic triglyceride measurements were correlated with a biochemical determination of TG for the rats - Fatty and Lean Zucker rats. There is a progressive increase in pTG along with glucose levels in the Fatty Zucker rats, but no change in either levels in the lean rats. Figure B shows the correlation between the MRS technique and biochemical determination.

Humans were divided into 4 groups and were scanned by MRS as well. The results are as in the abstract. Intereting findings included that blood glucose levels 2 hours after a glucose load were most closely correlated with pTG content. HBA1c, serum Tg, # of DM risk factors, age, BMI, fasting glucose, excercise, and dietary fat intake had either no or a weak relationship to pTG content.

Also of interest was the fact that there was little relationship between pancreatic and hepatic TG content (a previous report had shown a low correlation between hepatic and myocardial TG content).

What is not known is to what degree the TG deposition is related to Beta-cell damage/loss if at all? Also can medications, diet, weight loss or more severe caloric restriction reverse the pancreatic TG deposition and if so can this lead to a new B-cell production?

Nerd Alert:: iPhone to BP cuff

The ultimate melding of tech and medicine:

Check out more from the:

iPhone OS 3.0 preview event

Wal-Mart Says Will Sell E-Records to Doctors

From Medscape (you may have to log-in)

"WASHINGTON (Reuters) Mar 11 - Wal-Mart Inc, which has moved into low-cost healthcare with walk-in clinics and cheap prescriptions, said on Wednesday its Sam's Club unit would sell a package including software and Dell computers directly to doctors for electronic medical records."

Sounds good right. After all Wal-Mart has $4 prescriptions.

But check out the cost: "Medical software company eClinicalworks will offer the software program, Koehler said. She said the package would cost the first doctor in a practice about $25,000, with each additional user costing around $10,000."

No independent or small practice should pay that much for a medical record system. I think that EMR is one of the greatest scams around. Personally, I use Soapware which has worked reliably for the past 2 1/2 years without a single lost or problem record. True Soapware has gone up in price - from $400 to $1200 a year, but it's still nearly 20+ times cheaper. Even cheaper, if you don't mind your EMR being completely on the internet, Office Ally offers an EMR for $24.95 a month. A colleague of mine uses it and thinks it's great.

Now the cost of the Wal-Mart/Sam's Club EMR does include hardware, software, and installation, but unless the hardware is worth about $23,000, I am dubious about this system.

Diabetic foot exam - plantar fasciitis

I saw a 47 yo patient today with DM2. She was complaining of L heel pain for 1 month. She wakes up with pain and it is present all day long. There was no cracking, redness, warmth, etc. She had no history of trauma. She has had some minor symptoms of numbness in both feet. B DP 1+. Ankle reflexes 2+. LT and vibration intact B. I found a nice picture from uptodate submitted by Robert P Sheon, MD of a test to elicit plantar fasciitis pain. This maneuver - which involves grasping and dorsiflexing the toes with one hand while palpating the plantar foot with the other hand - did in fact elicit pain. I am also ordering plain films, but I thought that this was a nice and simple test to perform for diabetics with otherwise unexplained plantar or heel pain.

Diabetic Retinopathy and VEGF antibody

From NEJM Feb 26, 2009

Here's your authrorization!

I don't want to ruin the clinical/scientific spirit of the blog by weighing it down with the daily idiocy of medical practice (I'm considering making a separate blog for that, let me know what you think), but I have to vent.

I have prescribed sensipar for a patient with primary hyperparathyroidism who was not a surgical candidate. I've prescibed it for 3 days a week (in a rather overcautious way perhaps to avoid potential hypocalcemia), and now want to increase the dosing to every other day. I originally filled out an authorization for the 3 day a week dosing and it was approved. Now the insurance company wants me to fill out a completely new authorization form for this minor change in dose frequency.

Here is My authorization:

• 12 years of Grade School
• 4 years towards a Bachelor of Science Degree
• Qualifiying MCAT scores
• 4 Years of Medical School
• 3 USMLE exams
• 3 years of Internal Medicine Residency
• Board Certification in Internal Medicine
• 2 years Endocrinology fellowship (where I learned how to spell sensipar)
• Board Certification in Endocrinology, Diabetes, and Metabolism
• Numerous awards, Grand Rounds, etc.

In other words I really don't need to fill out any G-- D--- authorization, because I make the decisions not these zeros....

I have a work around which I'll post separately. When you've worked at LAC you know how to get around anything.

Viva Hypoglycemia!

Fascinating tidbit about an "outbreak" of hypoglycemia related to sexual performance enhancing drugs tainted with glyburide with tragic consequences from the NEJM.

(The tragic results are nothing to laugh about, but some of the names of these names of the drugs ought to automatically steer one clear: Power 1 Walnut, Santi Bovine Penis Erecting Capsule.)

DEXA challenge: Find the errors

It seems that at least one in 10 or maybe one in 20 DEXA scan reports that I read contain some typographical error regarding the reporting of T scores or BMD. It is important to recognize, because I have seen patients' therapy changed/started/stopped by referring physicians based on erroneous results that were missed. See if you can spot the errors here. I have called the radiologists to confirm the errors. There were two that I found.

Endcorine Bailout!

You knew it was coming - a piece of the bailout may be going to Endocrinologists. Yes even the lowly Endocrinologist and other physicians may be able to benefit from the Multi-billion dollar bonanza. (What you may not have known is that there is a bottomless pit of money hidden beneath the Treasury Building. Get out your shovels!)

Read more here.

VAP Panel sample

Here's a VAP in action:

Bromocriptine improves GH levels in Obesity

J Clin Endocrinol Metab. 2008 Sep;93(9):3455-61

CONTEXT: A profound reduction of spontaneous as well as stimulated GH secretion has been consistently observed in obesity. Dopamine promotes GH release through activation of dopamine D2 receptors (D2Rs). Dopamine D2R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that impaired dopamine D2R signaling is mechanistically involved in the deficient GH secretion associated with obesity.

OBJECTIVE: To test this hypothesis, we studied the effect of short-term bromocriptine (B) (a D2R agonist) treatment on spontaneous 24-h GH secretion in obese women, while body weight and caloric intake remained constant. DESIGN: This was a prospective, fixed order, cross-over study. SETTING: The study was performed in the Clinical Research Center at Leiden University Medical Center. PARTICIPANTS: There were 18 healthy obese women (body mass index 33.2 +/- 0.6 kg/m2) studied twice in the early follicular phase of their menstrual cycle. INTERVENTION(S): Eight days of treatment with B and placebo (Pl) was performed. MAIN OUTCOME MEASURE(S): Blood was collected during 24 h at 10-min intervals for determination of GH concentrations. GH secretion parameters were calculated using deconvolution analysis.

-------

The figure really shows what's going on here, so I omitted the rest of the abstract. You can see that giving bromcriptine restored the pulsatile secretion of growth hormone in these obese patients. Basal GH secretion was not enhanced and also IGF-1 levels were not significantly changed.

Interestingly, other studies have been done looking at the effects of bromocriptine on other parameters. Theses studies showed that 24-hour glucose, insulin, and leptin levels were significantly reduced, whereas FFAs were enhanced after bromocriptine treatment.

See also:
J Clin Endocrinol Metab. 2006 Aug;91(8):3236-40.
Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1038-43.

Copy to Clipboard added to PE tool

Physical Exam Tool v 0.1

A button has been added right on the page to make it easy to send the text of your newly created physical exam to the system clipboard. Then just paste it anywhere. Beats typing the full exam.

Of course if you're using traditional dictation, it doesn't matter. But if you need to type or even if you are using say Dragon Software for dictation, documenting an exam can be tedious, so this makes it easy.