Podcast Summary:

Healthier World with Quest Diagnostics
Episode: Laboratory Assessment in the Diagnosis of Male Hypogonadism
Date: June 5, 2024
Host: Dr. Mason Latsko
Guest: Dr. Sanjay Dixit, Board-Certified Endocrinologist and Medical Director, Quest Diagnostics
Duration: 16 minutes

Overview

This episode provides a practical and clinically grounded exploration of adult male hypogonadism, focusing on the importance of laboratory assessment in diagnosis. Dr. Sanjay Dixit walks through the clinical presentation, the laboratory workup recommended by current guidelines, and the crucial distinctions between primary and secondary hypogonadism. The discussion also touches on monitoring requirements during testosterone replacement therapy and the broader cardiometabolic implications of hypogonadism.

Key Discussion Points & Insights

1. Defining Adult Male Hypogonadism

• Definition: A syndrome resulting from decreased testosterone and/or sperm production due to testicular or hypothalamic-pituitary dysfunction (01:25).

• Prevalence: Estimated to affect 4–5 million men in the U.S.; prevalence rises with age and in those with diabetes or obesity (01:25, 02:03).

  “It's estimated that approximately 35% of men older than 45 are impacted by hypogonadism.”
  — Dr. Mason Latsko (00:28)

2. Clinical Signs and Symptoms

• Symptoms are often non-specific: decreased energy, low libido, erectile dysfunction, depressed mood, osteoporosis, reduced testicular size, and regression in sexual characteristics (02:16).

• Many symptoms overlap with other conditions, making laboratory confirmation essential (02:16).

  “Clinical symptoms are only part of the diagnosis. The laboratory assessment is the objective piece…”
  — Dr. Sanjay Dixit (02:16)

3. Stepwise Laboratory Assessment

Initial Workup

• Assess Patient Holistically: Rule out other illnesses and medications (notably opioids) that may lower testosterone (03:29).

• Start with Total Testosterone Testing (ideally by LC-MS/MS, the guideline-preferred, highly accurate method) (03:29).

  “LC-MS/MS is the preferred and guideline recommended methodology for assessment of total testosterone…”
  — Dr. Sanjay Dixit (03:29)

• Blood Draw Timing: Fasting, between 8 and 10 am; glucose ingestion can lower serum testosterone levels (04:33).

If Total Testosterone is Low

• Confirm with repeat total testosterone and obtain free testosterone (via equilibrium dialysis, the gold standard) (05:12–05:27).
• Diagnostic criteria: Low total and low free testosterone confirm hypogonadism in men <69 years (04:33).

When to Add Free Testosterone on Initial Panel

• In patients with conditions altering SHBG (sex hormone binding globulin): obesity, diabetes (↓ SHBG) or aging, hyperthyroidism (↑ SHBG) (05:27).

• In these cases, order total and free testosterone together.

  “Providers should consider ordering a total testosterone and a free testosterone at the same time in patients with any of these chronic conditions.”
  — Dr. Sanjay Dixit (05:27)

• Free Testosterone Measurement:

  • Gold standard: Equilibrium dialysis (06:44).
  • If unavailable, calculate based on total testosterone, SHBG, and albumin (06:53).

  “Immunoassay platforms are less accurate...and should not be used to measure free testosterone for a hypogonadism workup.”
  — Dr. Sanjay Dixit (06:53)

4. Differentiating Primary vs. Secondary Hypogonadism

• Order FSH and LH to determine level of dysfunction (07:41).

• Primary Hypogonadism (testicular): Low testosterone, high FSH and LH ("FSH and LH...shout at the testicles to release more testosterone" [09:14]).

• Secondary Hypogonadism (hypothalamic-pituitary): Low testosterone, low/inappropriately normal FSH and LH.

• Combined Hypogonadism: Both features, depending on which predominates.

  “In primary hypogonadism, you'll see a high FSH and LH. Contrast that to secondary...you would see a low or inappropriately normal FSH and LH.”
  — Dr. Sanjay Dixit (09:14)

5. Monitoring During Testosterone Replacement Therapy

• Discussion of therapy is individualized and beyond scope, but lab monitoring is crucial (10:52).

• Monitor:

  • Total testosterone (midway between IM injections or 2–8 hours after topical application)
  • Hematocrit
  • PSA (prostate-specific antigen)
  • Bone mineral density (if appropriate)

  “Monitoring of testosterone, hematocrit, and prostate specific antigen...is recommended…”
  — Dr. Sanjay Dixit (10:52)

• Timing: Re-assess at 3–6 months post-initiation (10:52).

6. Cardiometabolic Impact

• Hypogonadism is linked to increased risk of diabetes (4x higher), metabolic dysfunction-associated liver disease, hypertension, atherosclerotic cardiovascular disease, and elevated mortality (12:17).

  “Men who have a low testosterone level have four times greater risk of diabetes…”
  — Dr. Sanjay Dixit (12:17)

7. Algorithms, Resources, and Final Takeaways

• Quest Diagnostics offers a diagnostic algorithm aligned with guidelines.

• Consistently start with a total testosterone (preferably LC-MS/MS).

• Add/confirm with free testosterone, FSH, and LH as appropriate.

• Use equilibrium dialysis for free testosterone measurement when possible.

• Monitor patients on therapy as recommended by guidelines.

  “These symptoms are non specific, somewhat vague. The laboratory assessment is really the objective evidence you need to make diagnoses of any endocrine disorder, hypogonadism included.”
  — Dr. Sanjay Dixit (14:01)

Notable Quotes & Memorable Moments

| Timestamp | Quote | Speaker | |-----------|-------|---------| | 02:16 | “Clinical symptoms are only part of the diagnosis. The laboratory assessment is the objective piece...” | Dr. Dixit | | 03:29 | “LC-MS/MS is the preferred and guideline recommended methodology for assessment of total testosterone...” | Dr. Dixit | | 05:27 | “Providers should consider ordering a total testosterone and a free testosterone at the same time in patients with any of these chronic conditions.” | Dr. Dixit | | 09:14 | “In primary hypogonadism, you'll see a high FSH and LH. Contrast that to secondary...you would see a low or inappropriately normal FSH and LH.” | Dr. Dixit | | 10:05 | “FSH and LH are basically shouting at the testicles to release more testosterone. But because the issue is at the level of the testes, the testes basically aren't listening.” | Dr. Latsko | | 14:01 | “The laboratory assessment is really the objective evidence you need to make diagnoses…hypogonadism included.” | Dr. Dixit |

Timestamps for Important Segments

• 00:28 – Prevalence and clinical impact of hypogonadism
• 01:25 – What is adult male hypogonadism?
• 02:16 – Key clinical signs and symptoms
• 03:29 – Laboratory assessment and preferred methodology
• 05:27 – When to order free testosterone
• 06:53 – Free testosterone measurement: Gold standard and alternatives
• 07:41 – Differentiating primary vs secondary hypogonadism (FSH/LH interpretation)
• 10:52 – Lab monitoring during testosterone therapy
• 12:17 – Cardiometabolic risks & broader health impacts
• 14:01 – Final takeaway: The centrality of lab assessment

Final Takeaways

• Symptoms of hypogonadism are often vague and overlap with other disorders; lab assessments are critical for accurate diagnosis.
• Start with total testosterone by LC-MS/MS; add free testosterone and gonadotropins (FSH/LH) as needed.
• Equilibrium dialysis is the gold standard for free testosterone; calculated values are an alternative if unavailable.
• For those on replacement therapy: monitor total testosterone, hematocrit, and PSA as per guidelines.
• Hypogonadism is associated with increased cardiometabolic risk and should be taken seriously by providers.

For further learning:

• Refer to the diagnostic algorithm and clinical focus in the podcast description.
• Explore the Quest Diagnostics Clinical Education Center for more resources.