hyperparathyroidism treatment

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hypercalcemia/

Indications for Treatment.

Removal of the abnormal and hyperfunctioning parathyroid tissue results in a long-term cure of HPT in 96% of patients and significant improvement in associated symptoms. The following criteria were proposed as indications for parathyroidectomy based on a National Institutes of Health–sponsored panel and endocrine specialty societies: ⁷

1. Serum Ca level more than 1 mg/dL above the upper limit of normal
2. Marked hypercalciuria higher than 400 mg/day
3. Creatinine clearance reduced more than 30% compared with age-matched controls
4. Reduction in bone mineral density of the femoral neck, lumbar spine, or distal radius of more than 2.5 standard deviations below peak bone mass (T score lower than -2.5)
5. Age younger than 50 years
6. Patients for whom medical surveillance is not desirable or possible
7. Presence of any complications (e.g., nephrolithiasis, overt bone disease)
8. An episode of hypercalcemic crisis

However, because no effective medical therapy for HPT exists, all patients with HPT who are otherwise healthy for surgery should be referred for surgical treatment.

Surgical Treatment.

Parathyroid surgery remains the single most effective treatment option in HPT and requires removal of all abnormal parathyroid tissue. Traditionally, in the vast majority of U.S. practices, this has meant bilateral exploration of the neck to identify all (typically four) parathyroids, assess which ones are abnormal, and remove only the abnormal glands. The setting of multiglandular hyperplasia requires subtotal parathyroidectomy or total parathyroidectomy, with reimplantation of parathyroid tissue into the sternocleidomastoid or forearm muscles. The parathyroids may then also be cryopreserved as a safeguard against future hypocalcemia, in which case the patient may undergo autotransplantation of autogenous, stored parathyroid tissue. In experienced hands, this approach has an exceptional rate of successful long-term cure of HPT (more than 96%) and a low rate of surgical complications (hypocalcemia less than 1%, recurrent laryngeal nerve injury 2% to 5%, neck hematoma or infection less than 1%). ⁸

In recent years, parathyroid procedures have been developed using smaller incisions under sedation and local anesthesia, and with the opportunity for outpatient surgery. Minimally invasive parathyroid surgery has become more frequently requested by patients and primary care physicians alike, even though it does not represent a uniform set of techniques. Depending on regional practices, minimally invasive parathyroid surgery can include laparoscopic, radio-guided or, most frequently, only unilateral neck surgery. The success of these approaches in curing HPT and minimizing complications is relatively unknown because clinical follow-up periods are still short. Minimally invasive parathyroid surgery is appropriate only for patients who have a single, clearly defined parathyroid abnormality on ultrasound, sestamibi scan, or both and when parathyroid hormone levels can be monitored intraoperatively. Bilateral neck exploration is mandatory in all other cases and for patients with familial or genetic syndromes.

Medical Treatment.

Patients who are not treated surgically should be managed to ensure good hydration and to avoid thiazide diuretics. Ambulation should be encouraged. Calcium intake should be average, because excessive intake may aggravate hypercalcemia, especially in patients with high calcitriol levels, whereas low calcium intake may stimulate PTH secretion. Bisphosphonates may be used to lower the serum calcium level in patients with symptomatic hypercalcemia (see later, “Treatment of Hypocalcemia”), although they are usually not effective.

beta blockers in COPD

It has been a looong gap ....moving and starting a fellowship in a new place is a little tough. Anyway I have settled down in my new place now. 

Let me start with a short blog..regarding a discussion between a pulmonary fellow and the primary team that I happened to hear while doing my usual hyponatremia consult!

Traditionally betablockers were not used in patients with COPD or asthma due to bronchospam. But using a cardioselective agent may not afect the airways.But a recent retrospective study in bmj went a step ahead and showed that it may be even beneficial in patients with COPD. 

Of nearly 6000 patients with different stages of COPD ,they found that there was a 22% reduction in all cause mortality from beta blockers. The benifit was shown across all stages of COPD. With regards to lung function, they did not affect FEV1/FVC. also betablockers seemed to have additive benifits on hospital admissions. This benifit was seen independent of presence of cardiovascular disease.

A somewhat related study published by one of my senior resident(Int J Chron Obst Pulm Disease 2010)  showed that patients with COPD may have unrecognised myocardial injury. May be betablockers help with this and this is what we are seeing here. 

Time to change practice!!

Osteoporosis --- Screening & Treatment

Osteoporosis is very much underdiagnosed, and under treated! I recently did my practice based learning exercise on Osteoporosis, and sadly...I havent screened or treated many of my patients!!


So lets see who needs to be screened, and who needs treatement...
DEXA Scan and scoring  - Screening /diagnosing is done by DEXA scan . The 2 preferred sites of scanning are lumbar spine and proximal femur,as these places show the earliest sign of osteoporosis. So next time when you see a score based on a heel DEXA ....it is not a complete test! A T-score( representing the number of standard deviations between the pts bone mineral density and a healthy young adult of same sex) less than -2.5 is called osteoporosis, and a score between -1 to -2.5 is osteopenia. 
The Z-score is used to classify the type of osteoporosis. A score below 1.5 indicates primary osteoporosis, which is age related. A score of 1.5 and higher indicates secondary osteoporosis, which is associated with calcitonin imbalance, malabsorption conditions ,alcohol abuse, smoking, medications etc.


Screening - The following are the group of people who need DEXA for screening

• women 65yrs and older,
•  men 70 yrs and older,
• Loss of height of >2 inches (before DEXA...do a vertebral fracture survey...and if +ve, treat as osteoporosis)
• postmenopausal women or, men >50 yrs with risk for fracture including h/o hip fracture in parents, current smoker or alcoholic, rheumatoid arthritis.
• chronic glucocorticoid therapy(5mg/d or more of prednisone for >3 mon)
• pts with medical diseaseassociated with decreased BMD(eg. renal disease, hyperthyroisim, cushings etc)
• pts on medications that might reduce BMD ( anticonvulsants, PPI,Cyclosporine, SSRI etc

Who needs treatment -  

• Anyone who has sustained a fragility fracture of hip or spine
• Those who have a T-score > or = 2.5, after evaluation for secondary causes of osteoporosis.
• Those who have osteopenia(a score between -1 & -2.5) if their 10 year probablity of osteoporotic fracture is >20% or 10 yr risk of hip fracture >3%. ( the risk called FRAX ..can be calculated online)

Treatment -  Bisphosphonates are the mainstay of treatment. A quick note is...of all the treatment modalities, Ibandronate, Calcitonin, Raloxifene, and Teriparatide are the ones which have not shown any hip fracture reduction. All of them reduce the incidence of spine fracture though.

Pre exposure prophylaxis for HIV

A homosexual male who is an iv drug abuser walks into the office...asking ways to help him prevent contacting HIV..with his high risk behaviour!! Apart from advising on safe sex and risks of sharing needles(which are most important..and at the same time cannot be relied at all times due to non adherence)....do we have any medications to offer him??


Lets look at the iPREX study published in NEJM Dec 2010. This was a placebo-controlled, double-blind, randomized trial involving 2499 subjects(men who have sex with men) to see if a combination of Emtricitabine-Tenofivir(FTC-TDF) once daily reduced the incidence of HIV over a f/u period of 1.2 years. Of the 100 incident HIV infections during the study period, 64 occurred in the placebo group and 36 in the FTC–TDF group, with an efficacy of 44% and a 95% CI of 15 to 63. An important finding to note is that, in the FTC–TDF group, the study drug was pharmacologically detected in 51% of subjects who remained free of HIV infection but in only 9% of those who became infected. So exposure to FTC–TDF was associated with a reduction in HIV acquisition. Main issues in putting this into practice has a few concerns. Few of them are drug adherence(very poor in the study), long term outcome, side effects(quite a few in the study drug group had renal impairement which rverted to normal on discontinuation of drug!). All these issues have been nicely discussed in the letter following the study( another arrow in the Quiver.NEJM Dec 2010)
Now the trial has been extended to look for long term outcomes and ways to improve adherence. results are expected by 2013.(HIV & TB News)


An earlier study , CAPRISA 004 in which a total of 889 sexually active, HIV-uninfected women (age range, 18–40) received either 1% tenofovir gel or placebo gel, with instructions to administer the gel intravaginally within 12 hours before sex and also within 12 hours after sex. Mean follow-up was 18 months.The incidence of HIV was 5.6 /100 person-years in the tenofovir group versus 9.1 /100 person-years in the placebo group, for an incidence rate ratio (IRR) of 0.61 (95% CI, 0.40–0.94; P=0.017). Shows promise for pre exposure prophylaxis.


In this context ...FEM-PrEP trial has to be mentioned. This study evaluated if oral daily FTC-TDF prevented HIV in a group of high risk women. The study was stopped last month after an interim analysis didnt find any benefit compared to placebo.(AVAC April 2011). Full analysis of trial should be available shortly.(may be related to adherence issues!!)


VOICE trial - Vaginal and Oral Interventions to Control the Epidemic .........is an ongoing study on high risk women comparing FTC-TDF, tenofovir tablet alone , or tenofovir gel. This study might shed light into ..which of these will be more effective. By this time we will also have the long term safety and compliance outcomes on the i-PREX study.
May be 2013 might be a year the world would see a...  'HIV prevention pill'  !!!

The "aura" of migraine

Migraine can be with or without aura. What exactly comprises this aura. The prodromal  and associated  migraine symptoms may me mistaken as aura. Lets see what comprises the so called aura.  It is the migraine with aura that is related to an increased incidence of ischemic stroke, and is a contraindication for taking oral contracptives!(as risk of stroke increases 4 fold in this population)

The migraine aura is a complex of neurologic symptoms that may precede or accompany the headache phase or may occur in isolation. It usually develops over 5-20 minutes and lasts less than 60 minutes. The aura can be visual, sensory, motor, or any combination of these.

Auras most commonly consist of visual symptoms, which may be negative or positive. Negative symptoms include negative scotoma, homonymous hemianopic or quadrantic field defects, central scotomas, tunnel vision, altitudinal visual defects, or even complete blindness.The most common positive visual phenomenon is the scintillating scotoma. This consists of an arc or band of absent vision with a shimmering or glittering zigzag border. It is often combined with photopsias or visual hallucinations, which may take various shapes.Scintillating scotoma is a highly characteristic syndrome that always occurs prior to the headache phase of an attack and is pathognomonic of a classic migraine.Other positive visual phenomena include photopsia (uniform flashes of light) or simple forms of visual hallucinations. Heat waves, fractured vision, macropsia, micropsia, and achromatopsia may also occur.

Paresthesias, occurring in 40% of cases, constitute the next most common aura; they are often cheiro-oral with numbness starting in the hand, migrating to the arm, and then jumping to involve the face, lips, and tongue. As with visual auras, positive symptoms typically are followed by negative symptoms; paresthesias may be followed by numbness. Sensory aura rarely occurs in isolation and usually follows visual aura. 

Motor symptoms may occur in 18% of patients and usually are associated with sensory symptoms. Motor symptoms often are described as a sense of heaviness of the limbs before a headache but without any true weakness.Speech and language disturbances have been reported in 17-20% of patients. These disturbances are commonly associated with upper extremity heaviness or weakness.

The migrainous aura generally resolves within a few minutes and then is followed by a latent period before the onset of headache.When an aura is not followed by a headache, it is called a migraine equivalent or acephalic migraine. This is reported most commonly in patients older than 40 years who have a history of recurrent headache.
Again....all this means...that we need a more detailed history from these patients to elicit these findings!!

Headache - - Trigeminal autonomic cephalalgias!!

Lets talk some neurology, as this month Iam doing neurology! When discussing headache, we came across this entity called  'Trigeminal autonomic cephalgias' -- a group of headache disorders with pain referred to the 1st branch of trigeminal nerve associated with cranial autonomic symptoms including lacrimation, injection of the eye and rhinorrhea. They all share the same pathophysiologic etiology....which is largely unknown!!! But there is some eveidence of posterioir hypothalamus in modulating this craniofacial pain, as found out by functional imaging of brain (Lancet 2009)There are 3 types, and they vary in their frequency and duration..

1.Cluster headache - 1 to 8 attacks per day with the mean duration of each attack being 60 min.
2.Paroxsmal hemicrania -  11 to 15 attack per day with a mean duration 15 min/attack
3.SUNCT syndrome (Short lasting Unilateral neuralgiform headache with Conjuctival injection and Tearing) - roughly 20 atatcks per day with a mean duration  of 30 sec to 2 min/attack.

Well this sounds like, that someone just wanted to classify them to make it difficult for others to remember. But it turns out that differentiating these 3 on the basis of duration is important as treatment options are different!
*Indomethacin works well in paroxysmal hemicrania(PH) and SUNCT, whereas it does not help patients with Cluster headache(CH).
*Sumatriptan and Oxygen can help CH, whereas they dont help PH & SUNCT
*For prophylactic treatment for CH, PH, & SUNCT...the drug of choice are Verapamil, Indomethacin & Lamotrigine respectively.
Have a look at this article from UK which explains in detail about these 3 headaches. Especially peek at the table on page 118.(Current Neuro & neurosci report 2007). Looks like ..we may need to be more specific with timing and duration of headaches, as we do for evaluation of chest pains!

Elevated pulse pressure and white coat effect

Can we differentiate white coat effect from true hypertension in the office?
Difficult(we usually need either a 24 hr ambulatory BP monitoring or frequent home BP measurements.....both of which are cumbersome, and cant be done regularly).....but may be possible.....says Dr.Ahn from Korea, when he presented his study in the American College of Cardiology Scientific sessions earlier this month. Lets see what they found out..

They took 1087 outpatients with chronically treated hypertension, and checked home BP twice daily for 2 week, and then checked it in the office. White coat effect was defined as a difference between the physician's BP and the home BP of above 20 mm Hg systolic or 10 mm Hg diastolic BP. White-coat hypertension was found in 31% of patients. Pulse pressure of 60 mm Hg and above positively correlated with WCE by multivariate analysis. So the author concluded that... if a patient has an elevated BP reading in the clinic along with elevated pulse pressure, we can consider WCE before recommending antihypertensive agents. 


Some other interesting associations from the study : 
1. White-coat hypertension was not associated with age or gender in the study, 
2. Those with a family history of premature coronary disease were more likely to display WCE.
3. Those with diabetes or organ damage including the heart, as well as smokers, were less likely to show WCE.


The positive relationship with family history might be the result from the effects of anxiety and emotional stress, and the negative relationship with diabetes or smoking means that the WCE was relatively benign in these patients. Also pts with diabetes and organ damage may not be able to mount a stress response due to autonomic imbalance, LV dysfuction etc.


Is this important? Well.... it is...as we all know that white coat hypertension is a predecessor for chronic hypertension, as based on the findings from Italy(Hypertension 2009) ...in which thy followed nearly 1400 pts with white coat or masked hypertension , and found that 40% of patients with white coat effect progressed to develop Hypertension over a period of 10 years. So..YES...WHITE COAT HYPERTENSION needs to be identified and monitored closely. We usually dont treat WCH due to risk of hypotension...but they need to be monitored closely for development of hypertension.