Hypogonadism and right ventricular failure with testosterone deficiency myopathy

A 30 YEAR OLD WITH BILATERAL PEDAL EDEMA AND DYSPNEA ON EXERTION 

I've been given this case data to solve in an attempt to understand and analyize the topic based on patient clinical data in order to develop competency in reading and comprehending clinical data related to the case and come up with a suitable diagnosis.

You can find the original case in the link below-

https://saikiranpatnam.blogspot.com/2020/05/medicine-case.html?m=1

FOLLOWING IS THE PROBLEM LIST ACCORDING TO PATIENT'S PRIORITY:

MAIN COMPLAINTS:

 1. Bilateral pedal edema

 2. Dyspnea on exertion

 3. Papitations

 4. Decreased urine output

 5. Dry Cough

EACH COMPLAINT IN DETAIL:

  1.Bilateral pedal edema:

• Since 15 days

• Upto knees

• PROBABLE CAUSE:

• Heart Failure
• Liver disease -- ruled out as there is no ascites
• Malnutrition --ruled out as there is no abdominal distention
• Renal cause --ruled out as there is no facial puffiness
• Thyroid disorder --rare

  2. Dyspnea on exertion:

• Since 15 days

• Past history: first became breathless on walking for short distance and while going upstairs

• There is also a history of nocturnal wheezing

• Not associated with orthopnea/PND

• PROBABLE CAUSES:

• Respiratory cause( COPD,Pneumonia)
• Anemia
• Renal cause --ruled out as there is no symptoms like facial edema
• Heart failure

 Source: https://www.slideshare.net/muhammadhelmi37853/dyspnoea-respiratory-failure

3. Papitations:

• Since 1 year

• Persistent, Pounding type

• Aggravated by EXERTION

• Relieved on REST

• POSSIBLE CAUSES:

1. Cardiac causes:Mitral valve prolapse,pericarditis,congestive heart failure
2. Non-cardiac causes:Hyperthyroidism, hypoglycemia 

 

4.Decreased urine output:

• Since 2 days

• POSSIBLE CAUSES:

• Dehydration
• Kidney failure
• Heart failure--can lead to renal failure

 5.Dry Cough:

• Since last 15 days

• No expectoration

• POSSIBLE CAUSES:

• Allergic rhinitis -- ruled out as there are no symptoms like sneezing and runny nose and so no history of allergies
• Pneumothorax --ruled out as there is no pleuritic pain
• Pulmonary embolism -- ruled out as there is no hemoptysis
• Heart failure

No H/O hemoptysis

No increase in frequency in micturition

PAST HISTORY:

• No similar complains in the past
• Not a known case of HTN,Diabetes,EPILEPSY,CVA,CAD

FAMILY HISTORY:

• No similar complaints in the family

PERSONAL HISTORY:

• Mixed diet
• Appetite and sleep -- decreased
• No addictions, no allergies

GENERAL EXAMINATION:

• He is consious,coherent and cooperative,moderately built and nourished
• Afebrile
• Pallor absent
• No Icterus,cyanosis,clubbing,lymphadenopathy
• EDEMA: B/L pitting type of pedal edema upto knees
• BP:120/70mmHg
• RR:20cpm
• PR:124bpm
• Undescended testis(cryptochidism)
• Very less facial hair+less pubic hair+no axillary hair=Tanner Stage 4

ON EXAMINATION:

RESPIRATORY SYSTEM

• Bilateral air entry +

• Normal vesicular breath sounds

CVS

• Visible pulsation over Tricuspid and Mitral areas

• Apex beat felt over V intercostal space within Midclavicular line -- foreceful and well sustained

• Right Ventricular Heave +

• JVP raised with prominent 'a' wave

• S1, S2 heard with prominent P2

CNS

• Conscious, coherent, cooperative, well oriented to time,place and person

• High mental functions=Normal

• Minimental Score = 28 --> Normal cognition

• High-Stepping Gait

• MOTOR SYSTEM:

• Bulk, Tone - Normal
• Power: slightly low in Lower limbs>Upper limbs
• Reflexes: Present
• SENSORY SYSTEM:
• Anterolateral and dorsal tract senses - INTACT
• Tactile sensation - NORMAL
• Two point discrimination - IMPAIRED in LOWER LIMBS
• Skull, spine -Normal
• No cerebellar or meningeal signs

ABDOMEN: Normal, bowel sound present

INVESTIGATIONS SHOWED:

• T3 levels -- slightly low

• FBS levels -- slightly high

• ALP levels -- High

• Albumin in urine - Present

• Low RBC count, hemoglobin, PCV

• USG: Raised echogenicity of B/L Kidneys

• Colour doppler 2D Echo:

• Valves - Normal
• Right atrium and ventricle -- Dilated
• Inferior vena cava-- Mildly dilated
• Tachycardia
• Mild AR, Moderate TR, Trivial MR
• Good LV systolic function
• No AS/MS, No PAH/PE

• ECG:

• X-Ray:

• USG Scrotum:
• B/L Scrotal sac empty 
• Both testes not found in B/L inguinal region
• Prostate - Present
• Urinary bladder - partially distended

ANATOMICAL LOCATION OF THE ROOT CAUSE:

• Bilateral Pedal edema is not associated with facial puffiness and no ascites --thus renal cause and hepatic disease ruled out

• Dyspnea is on exertion and is associated with dry cough and not associated with orthopnea

• Palpitations are pounding type and associated with shortness of breath indicating the cause being the HEART

• Dry Cough is not associated with hemoptysis,sneezing,runny nose or H/O hemoptysis -- thus allergic rhinitis and pulmonary embolism can be ruled out

In view of the above points,i am of the opinion that the pathology lies in the HEART,most probably HEART FAILURE

Which sided heart failure??

• 2D ECHO findings:

• Valves - Normal
• Right atrium and ventricle -- Dilated
• Inferior vena cava-- Mildly dilated
• Tachycardia
• Mild AR, Moderate TR, Trivial MR
• Good LV systolic function
• No AS/MS, No PAH/PE

• JVP: elevated with prominent 'a' wave -- 

SOURCE https://www.ncbi.nlm.nih.gov/books/NBK300/ says --

"There are only two causes of giant a waves: decreased right ventricular compliance or tricuspid stenosis. Causes of the former are pulmonary valve stenosis, chronic obstructive pulmonary disease with associated pulmonary hypertension, or restrictive cardiomyopathy, each of which decreases right ventricular compliance. In these conditions the force of right atrial contraction is increased and generates a giant a wave during atrial systole. As pulmonic valve stenosis and tricuspid stenosis are uncommon diseases in adults, giant a waves almost invariably indicate either pulmonary arterial hypertension or a restrictive cardiomyopathy involving the right ventricle."

Thus, it is most probably RIGHT VENTRICULAR FAILURE.

• The right ventricular failure may be primarily due to pulmonary hypertension. 

PHYSIOLOGICAL FUNCTIONAL DISABILITY:

According to the source-https://www.verywellhealth.com/symptoms-and -complications-of-heart-failure-4161320

• "With heart failure, the pumping of the heart is less efficient than normal. To compensate for this reduced pumping ability the body attempts to hold on to salt and water. The accumulation of sodium and water can initially improve cardiac function, at least marginally—but eventually, fluid accumulation becomes excessive and leads to several kinds of symptoms."

• In heart failure, the body’s accumulation of salt and fluid produces increased pressures in the cardiac chambers. Elevated cardiac pressure causes some of that excess fluid to accumulate in the lungs. The result is lung congestion.

• This lung congestion typically causes breathing difficulties that can produce several distinct symptoms such as Dyspnea on exertion, Dry cough

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512682/  says--"Testosterone (T) has a number of important effects on the cardiovascular system."

• Certain sources say--https://pubmed.ncbi.nlm.nih.gov/29712743/

"The association of sex hormone (estradiol, testosterone, and progesterone) with cardiopulmonary disease has already attracted great attention, especially in pulmonary arterial hypertension (PAH). However, the impact of sex hormones and their pituitary stimulators (follicle-stimulating hormone and luteinizing hormone) on PAH in men remains unclear. We conducted a prospective cohort study recruiting 95 patients with idiopathic PAH from 2008 to 2014 and following up for a median of 65 months for death. Compared with control, abnormal plasma levels of sex hormones were more common in patients with PAH. Higher estradiol and estradiol/testosterone levels were associated with risk of PAH diagnosis (odds ratio per ln estradiol, 3.55; P<0.001; odds ratio per ln estradiol/testosterone, 4.30; P<0.001), whereas higher testosterone and progesterone were associated with a reduced risk (odds ratio per ln testosterone, 0.48; P=0.003; odds ratio per ln progesterone, 0.09; P<0.001). Fifty patients died during follow-up. Men with higher estradiol had increased mortality (hazard ratio per ln estradiol, 2.02; P=0.007), even after adjustment for baseline characteristics and PAH treatment. According to receiver operating characteristic analysis, patients with PAH with higher estradiol level (≥145.55 pmol/L) had worse 5-year survival rate compared with those with lower estradiol (38.6% versus 68.2%; log-rank test P=0.001). Therefore, our data show higher estradiol, estradiol/testosterone ratio, lower testosterone, and progesterone were associated with increased risk of PAH. Meanwhile, higher estradiol was independently associated with higher mortality in men with PAH. Further studies are needed to explain the origin of these hormonal derangements and their potential pathophysiological implications in PAH."

Thus,Hypogonadism that leads deficiency of testosterone in males can cause Pulmonary artery Hypertension.

• Hypogonadism can have certain neurological features

Hypogonadism has remarkable associations with variable medical disorders; however, it is characterized by a distinctive association with variable neurological disorders: such as epilepsy, ataxia, dysmyelination, nerve muscle disease, movement disorders, mental retardation and deafness. The remarkable neurological diseases with hypogonadism should not basically be regarded as coincidental findings, but possibly related to an intrinsic pathophysiological association.

REFERENCE: https://pubmed.ncbi.nlm.nih.gov/23292617/ 

• Also, decreased testosterone levels can lead to the so called TESTOSTERONE DEFICIENCY MYOPATHY according to a journal-https://www.researchgate.net/publication/15635947_Testosterone_deficiency_myopathy

• Hypogonadism can change the calf muscle elasticity thus causing muscle weakness in the lower limbs--REFERENCE: https://eje.bioscientifica.com/view/journals/eje/156/6/1560673.xml

ETIOPATHOGENESIS: 

https://www.sciencedirect.com/science/article/pii/S0735109716369133

https://www.sciencedirect.com/science/article/pii/S0735109713058701

DIAGNOSIS:

• Right ventricular failure with primary Pulmonary artery hypertension due to hypogonadism

• Hypogonadism (tanner stage 4)

• Lower limb proximal myopathy

• Oral candidiasis with poor oral hygiene 

• impaired glucose tolerence

TREATMENT:

• PHARMACOLOGICAL:
• Tab. Pantop 40 mg po/ OD
• Inj. Lasix 20 mg iv/ BD
• Inj. Thiamine 1amp. in 100 ml NS
• Inj. Optineurin 1amp in 100 ml NS
• Tab sildenafil 10mg po OD
• Tab benformet plus od
• On diuretic therapy and vaso dilator therapy patient got better and discharged in stable condition

• NON-PHARMACOLOGICAL:
• Fluid and salt restriction
• Diet according to Harvard plate

TREATMENT SUGGESTED:

• Primarily, Testosterone hormone replacement therapy and medication for the heart failure may can solve the problem in this patient.

ADVICE AT DISCHARGE:

• Fluid (1.5 to 2 L/day) and salt (2 gm /day) restriction
• Tab sildenafil 10 mg po/bd
• Tab benformet po/OD for 2 weeks
• Chlorhexidine oral gargles for two weeks
• Oral candid paint
• Diet according to Harvard plate 
• Work up for FSH,LH,GNRH
• Review after 2 weeks

REFERENCES:

• https://www.slideshare.net/muhammadhelmi37853/dyspnoea-respiratory-failure

• https://www.ncbi.nlm.nih.gov/books/NBK300/

• https://www.verywellhealth.com/symptoms-and -complications-of-heart-failure-4161320

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720171/

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720171/

• Davidsons principles of medicine

• https://pubmed.ncbi.nlm.nih.gov/23292617/ 

• https://www.researchgate.net/publication/15635947_Testosterone_deficiency_myopathy

• https://www.sciencedirect.com/science/article/pii/S0735109716369133

• https://www.sciencedirect.com/science/article/pii/S0735109713058701

Active learning and conversational decision support to treating team of this case:

[5/30, 13:51] MBBS 2016 UG 3: Sir...in the 30 yr old patient...he has a high stepping gait which indicates peripheral neuropathy

[5/30, 13:52] MBBS 2016 UG 3: But the diagnosis in his case report says that he has proximal lower limb myopathy

[5/30, 13:52] MBBS 2016 UG 3: Sir...in that case...he should be have waddling gait??

[5/30, 13:54] MBBS 2016 UG 3: This indicates that he should be having distal weakness

[5/30, 16:49] Post Residency PG1: Yes very good point. 

Please enter that query onto your log and also share with the treating team 👍👏👏

[5/30, 16:58] MBBS 2016 UG 3: Ok sir👍

[5/30, 16:59] Post Residency PG1: Can you share the patient's intern log link?

[5/30, 17:00] MBBS 2016 UG 3: Yes sir

[5/30, 17:01] MBBS 2016 UG 3: https://saikiranpatnam.blogspot.com/2020/05/medicine-case.html?m=1

[5/30, 17:16] Post Residency PG1: Absolutely chuffed to inform that Sai Kiran, our intern from previous batch has shared a link suggesting low testosterone levels could increase risk of PAH. 

Because of his profound thinking, I went ahead and searched if the link really is true. This is what I found. 

Patients with PAH also had lower testosterone (8.63 vs 14.13 ng/mL; P =.02) and progesterone (0.32 vs 0.68 ng/mL; P <.001) levels compared with controls.

Having higher estradiol and estradiol/testosterone levels was significantly associated with an increased risk for PAH (odds ratio per ln estradiol, 3.55; P <.001; odds ratio per ln estradiol/ testosterone, 4.30; P <.001). Conversely, having higher testosterone and progesterone were both associated with a reduced risk for PAH (odds ratio per ln testosterone, 0.48; P =.003; odds ratio per ln progesterone, 0.09; P <.001).

[5/30, 17:16] Post Residency PG1: 👏👏👍 Can we explain all his problems with hypogonadism? How do we explain his neurological findings? Also by guaging his current Tanner's status what would be the severity of his hypogonadism?

[5/30, 17:16] Post Residency PG1: Testosterone deficiency (<9.9 mmol/l) was found in 54% patients with a mean value of 8.63 in patients with idiopathic PAH. In age, sex and BMI matched controls, a mean TT value of 14.9 was observed. Seems significant to me.

[5/30, 17:20] MBBS 2016 UG 3: Yes sir

[5/30, 17:20] MBBS 2016 UG 3: Hypogonadism can have neurological features

[5/30, 17:20] MBBS 2016 UG 3: https://pubmed.ncbi.nlm.nih.gov/23292617/

[5/30, 17:20] MBBS 2016 UG 3: This link says it all sir

[5/30, 17:21] Post Residency PG1: 👍👏👏

[5/30, 17:22] Post Residency PG1: Please quote the portions relevant to our current patient

[5/30, 17:22] MBBS 2016 UG 3: Ok sir

[5/30, 17:34] Post Residency PG1: Anything more specific to our patient's neurological findings?

[5/30, 17:45] MBBS 2016 UG 3: Sir...this source https://eje.bioscientifica.com/view/journals/eje/156/6/1560673.xml says that there in change in calf muscles elasticity in hypogonadism

[5/30, 17:49] MBBS 2016 UG 3: And Sir...i also found a case of testosterone induced myopathy

[5/30, 17:54] MBBS 2016 UG 3: 

https://www.researchgate.net/publication/15635947_Testosterone_deficiency_myopathy

I've highlighted that point

[5/30, 17:57] Post Residency PG1: 👏👏👍

[5/30, 17:58] MBBS 2016 UG 3: Thank you sir